Chapter 48 Neurons Synapses and Signaling Reading Guide Answer Key

48 neurons, synapses, and signaling

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48 neurons, synapses, and signaling

1. 1061 48 Neurons, Synapses, and Signaling Lines of Communication The tropical cone snail (Conus geographus) in Figure 48.1 is small and slow- moving, yet it is a dangerous hunter. A carnivore, this marine snail hunts, kills, and dines on fish. Injecting venom with a hollow, harpoon-like tooth, the cone snail paralyzes its free-swimming prey in seconds. The venom is so deadly that unlucky scuba divers have died from just a single injection. What makes cone snail venom so fast acting and lethal? The answer is its mixture of toxin mol- ecules, each with a specific mechanism of disabling neurons, the nerve cells that transfer information within the body. Because the venom almost instantaneously disrupts neuronal control of locomotion and respiration, an animal attacked by the cone snail cannot escape, defend itself, or otherwise survive. Communication by neurons largely consists of long-distance electrical signals and short-distance chemical signals. The specialized structure of neurons allows them to use pulses of electrical current to receive, transmit, and regulate the flow of information over long distances within the body. In transferring information from one cell to another, neurons often rely on chemical signals that act over very short distances. The mixture of molecules in a cone snail's venom is particularly potent because it interferes with both electrical and chemical signaling by neurons. All neurons transmit electrical signals within the cell in an identical manner. Thus a neuron transmitting sensory input encodes information in the same way ▲ Figure 48.1 What makes this snail such a deadly predator? 1061 K E Y C O N C E P T S 48.1 Neuron structure and organization reflect function in information transfer 48.2 Ion pumps and ion channels establish the resting potential of a neuron 48.3 Action potentials are the signals conducted by axons 48.4 Neurons communicate with other cells at synapses ▲ Ribbon model of one example of a toxic peptide from cone snail venom
2. 1062 UNIT SEVEN Animal Form and Function as a neuron processing information or triggering movement. The particular connections made by the active neuron are what distinguishes the type of information being transmitted. Interpreting nerve impulses therefore involves sorting neu- ronal paths and connections. In more complex animals, this processing is carried out largely in groups of neurons orga- nized into a brain or into simpler clusters called ganglia. In this chapter, we look closely at the structure of a neuron and explore the molecules and physical principles that gov- ern signaling by neurons. In the remaining chapters in this unit, we will examine nervous systems, information process- ing, and the systems that detect stimuli and that carry out responses to those stimuli. The unit concludes by looking at how these functions are integrated in producing behavior. Dendrites Cell body Nucleus Synaptic terminals Synaptic terminals Axon hillock Axon Presynaptic cell Postsynaptic cell Synapse Neurotransmitter C O N C E P T 48.1 Neuron structure and organization reflect function in information transfer Our starting point for exploring the nervous system is the neuron, a cell type exemplifying the close fit of form and function that often arises over the course of evolution. Neuron Structure and Function The ability of a neuron to receive and transmit information is based on a highly specialized cellular organization (Figure 48.2). Most of a neuron's organelles, including its nucleus, are located in the cell body. A typical neuron has numerous highly branched extensions called dendrites (from the Greek dendron, tree). Together with the cell body, the dendrites receive signals from other neurons. A neuron also has a single axon, an extension that transmits signals to other cells. Axons are often much longer than dendrites, and some, such as those that reach from the spinal cord of a giraffe to the muscle cells in its feet, are over a meter long. The cone- shaped base of an axon, called the axon hillock, is typically where signals that travel down the axon are generated. Near its other end, an axon usually divides into many branches. Each branched end of an axon transmits information to another cell at a junction called a synapse (see Figure 48.2). The part of each axon branch that forms this specialized junction is a synaptic terminal. At most synapses, chemi- cal messengers called neurotransmitters pass information from the transmitting neuron to the receiving cell. In de- scribing a synapse, we refer to the transmitting neuron as the presynaptic cell and the neuron, muscle, or gland cell that receives the signal as the postsynaptic cell. The neurons of vertebrates and most invertebrates re- quire supporting cells called glial cells, or glia (from a Greek word meaning "glue") (Figure 48.3). Glia nourish neurons, insulate the axons of neurons, and regulate the extracellular fluid surrounding neurons. In addition, glia sometimes function in replenishing certain groups of neu- rons and in transmitting information (as we'll discuss later in this chapter and in Chapter 49). Overall, glia outnumber neurons in the mammalian brain 10- to 50-fold. ◀ Figure 48.2 Neuron structure. Arrows illustrate the flow of signals into, along, between, and out of neurons.
3. CHAPTER 48 Neurons, Synapses, and Signaling 1063 Introduction to Information Processing Information processing by a nervous system occurs in three stages: sensory input, integration, and motor output. As an example, let's consider the cone snail discussed earlier, fo- cusing on the steps involved in identifying and attacking its prey (Figure 48.4). To generate sensory input to the nervous system, the snail surveys its environment with its tubelike siphon, sampling scents that might reveal a nearby fish. During the integration stage, the nervous system processes input to determine if a fish is in fact present and, if so, where the fish is located. Motor output from the processing center then initiates attack, activating neurons that trigger release of the harpoon-like tooth toward the prey. Glia Cell bodies of neurons80 μm ▲ Figure 48.3 Glia in the mammalian brain. This micrograph (a fluorescently labeled laser confocal image) shows a region of the rat brain packed with glia and interneurons. The glia are labeled red, the DNA in nuclei is labeled blue, and the dendrites of neurons are labeled green. Integration Motor output Effector Processing center Sensor Siphon Proboscis Sensory input ▲ Figure 48.4 Summary of information processing. The cone snail's siphon acts as a sensor, transferring information to the neuro- nal circuits in the snail's head. If prey is detected, these circuits issue motor commands, triggering release of a harpoon-like tooth from the proboscis. Sensory neuron Interneuron Motor neuron Cell body Axon Dendrites ▲ Figure 48.5 Structural diversity of neurons. In these drawings of neurons, cell bodies and dendrites are black and axons are red. In all but the simplest animals, specialized populations of neurons handle each stage of information processing. Sensory neurons, like those in the snail's siphon, trans- mit information about external stimuli such as light, touch, or smell, or internal conditions such as blood pres- sure or muscle tension. Neurons in the brain or ganglia integrate (analyze and interpret) the sensory input, taking into account the im- mediate context and the animal's experience. The vast majority of neurons in the brain are interneurons, which form the local circuits connecting neurons in the brain. Neurons that extend out of the processing centers trig- ger output in the form of muscle or gland activity. For example, motor neurons transmit signals to muscle cells, causing them to contract. In many animals, the neurons that carry out integration are organized in a central nervous system (CNS). The neurons that carry information into and out of the CNS constitute the peripheral nervous system (PNS). When bundled to- gether, the axons of neurons form nerves. Depending on its role in information processing, the shape of a neuron can vary from simple to quite complex (Figure 48.5). Neurons that transmit information to many target cells do so through highly branched axons. Simi- larly, neurons that have highly branched dendrites can re- ceive input through tens of thousands of synapses in some interneurons.
4. 1064 UNIT SEVEN Animal Form and Function concentration of K+ is higher inside the cell, while the con- centration of Na+ is higher outside. The Na+ and K+ gradi- ents are maintained by the sodium-potassium pump (see Chapter 7). This pump uses the energy of ATP hydrolysis to actively transport Na+ out of the cell and K+ into the cell (Figure 48.6). (There are also concentration gradients for chloride ions (Cl- ) and other anions, as shown in Table 48.1, but we can ignore these for now.) The sodium-potassium pump transports three Na+ out of the cell for every two K+ that it transports in. Although this pumping generates a net export of positive charge, the resulting voltage difference is only a few millivolts. Why, then, is there a voltage difference of 60 to 80 mV in a rest- ing neuron? The answer lies in ion movement through ion channels, pores formed by clusters of specialized proteins that span the membrane. Ion channels allow ions to dif- fuse back and forth across the membrane. As ions diffuse through channels, they carry with them units of electrical C O N C E P T 48.2 Ion pumps and ion channels establish the resting potential of a neuron We turn now to the essential role of ions in neuronal signal- ing. In neurons, as in other cells, ions are unequally distrib- uted between the interior of cells and the surrounding fluid (see Chapter 7). As a result, the inside of a cell is negatively charged relative to the outside. Because the attraction of op- posite charges across the plasma membrane is a source of potential energy, this charge difference, or voltage, is called the membrane potential. For a resting neuron—one that is not sending a signal—the membrane potential is called the resting potential and is typically between -60 and -80 mV (millivolts). Inputs from other neurons or specific stimuli cause changes in the neuron's membrane potential that act as signals, transmitting information. Fundamentally, rapid changes in membrane potential are what enable us to see the intricate structure of a spiderweb, hear a song, or ride a bicycle. Thus, to understand how neurons function, we need to examine how chemical and electrical forces form, main- tain, and alter membrane potentials. Formation of the Resting Potential Potassium ions (K+ ) and sodium ions (Na+ ) play an essen- tial role in the formation of the resting potential. These ions each have a concentration gradient across the plasma membrane of a neuron (Table 48.1). In most neurons, the Key + K+ + – + –– + – + – + – – + Na+ Sodium channel Potassium channel Sodium- potassium pump OUTSIDE OF CELL INSIDE OF CELL ▲ Figure 48.6 The basis of the membrane potential. The sodium-potassium pump generates and maintains the ionic gradients of Na+ and K+ shown in Table 48.1. (Many such pump molecules are located in the plasma membrane of each cell.) Although there is a substantial concentration gradient of sodium across the membrane, very little net diffusion of Na+ occurs because there are very few open sodium channels. In contrast, the many open potassium channels allow a significant net outflow of K+ . Because the membrane is only weakly permeable to chloride and other anions, this outflow of K+ results in a net negative charge inside the cell. Ion Intracellular Concentration (mM) Extracellular Concentration (mM) + ) 140 + ) - ) 120 - 100 Table 48.1 Ion Concentrations Inside and Outside of Mammalian Neurons C O N C E P T C H E C K 4 8 . 1 1. Compare and contrast the structure and function of axons and dendrites. 2. Describe the basic pathway of information flow through neurons that causes you to turn your head when some- one calls your name. 3. W H AT I F ? How might increased branching of an axon help coordinate responses to signals communicated by the nervous system? For suggested answers, see Appendix A.
5. CHAPTER 48 Neurons, Synapses, and Signaling 1065 neuron? Consider a simple model consisting of two cham- bers separated by an artificial membrane (Figure 48.7a). To begin, imagine that the membrane contains many open ion channels, all of which allow only K+ to diffuse across. To produce a K+ concentration gradient like that of a mam- malian neuron, we place a solution of 140 mM potassium chloride (KCl) in the inner chamber and 5 mM KCl in the outer chamber. The K+ will diffuse down its concentration gradient into the outer chamber. But because the chloride ions (Cl- ) lack a means of crossing the membrane, there will be an excess of negative charge in the inner chamber. When our model neuron reaches equilibrium, the electri- cal gradient will exactly balance the chemical gradient, so that no further net diffusion of K+ occurs across the mem- brane. The magnitude of the membrane voltage at equi- librium for a particular ion is called that ion's equilibrium potential (Eion). For a membrane permeable to a single type of ion, Eion can be calculated using a formula called the Nernst equation. At human body temperature (37°C) and for an ion with a net charge of 1+, such as K+ or Na+ , the Nernst equation is Eion = 62mValog [ion]outside [ion]inside b Plugging the K+ concentrations into the Nernst equation reveals that the equilibrium potential for K+ (EK) is -90 mV (see Figure 48.7a). The minus sign indicates that K+ is at equilibrium when the inside of the membrane is 90 mV more negative than the outside. While the equilibrium potential for K+ is -90 mV, the rest- ing potential of a mammalian neuron is somewhat less nega- tive. This difference reflects the small but steady movement of Na+ across the few open sodium channels in a resting neuron. The concentration gradient of Na+ has a direction opposite charge. Any resulting net movement of positive or negative charge will generate a membrane potential, or voltage across the membrane. The concentration gradients of ions across the plasma membrane represent a chemical form of potential energy that can be harnessed for cellular processes (see Figure 44.17). Ion channels that convert this chemical potential energy to elec- trical potential energy can do so because they have selective permeability, allowing only certain ions to pass. For example, a potassium channel allows K+ to diffuse freely across the membrane, but not other ions, such as Na+ or Cl- . Diffusion of K+ through potassium channels that are al- ways open (sometimes called leak channels) is critical for establishing the resting potential. The K+ concentration is 140 mM inside the cell, but only 5 mM outside. The chemi- cal concentration gradient thus favors a net outflow of K+ . Furthermore, a resting neuron has many open potassium channels, but very few open sodium channels (see Figure 48.6). Because Na+ and other ions can't readily cross the membrane, K+ outflow leads to a net negative charge inside the cell. This buildup of negative charge within the neuron is the major source of the membrane potential. What stops the buildup of negative charge? The excess negative charges inside the cell exert an attractive force that opposes the flow of additional positively charged potassium ions out of the cell. The separation of charge (voltage) thus results in an electrical gradient that counterbalances the chemical concentration gradient of K+ . Modeling the Resting Potential The net flow of K+ out of a neuron proceeds until the chemi- cal and electrical forces are in balance. How well do these two forces account for the resting potential in a mammalian K+ Cl– Cl– Na+ Artificial membrane Potassium channel Inner chamber –90 mV Outer chamber +– +– +– Inner chamber Sodium channel +62 mV Outer chamber + + + – – – (a) Membrane selectively permeable to K+ (b) Membrane selectively permeable to Na+ 140 mM KCI 5 mM KCI 150 mM NaCI 15 mM NaCI EK = 62 mV log ––––––– = –90 mV 5 mM 140 mM Nernst equation for K+ equilibrium potential at 37°C: ENa = 62 mV log ––––––– = +62 mV 150 mM 15 mM Nernst equation for Na+ equilibrium potential at 37°C: ▶ Figure 48.7 Modeling a mammalian neuron. Each container is divided into two chambers by an artificial membrane. Ion channels allow free diffusion for particular ions, resulting in the net ion flow repre- sented by arrows. (a) The presence of open potassium channels makes the membrane selectively permeable to K+ , and the inner chamber contains a 28-fold higher concen- tration of K+ than the outer chamber; at equilibrium, the inside of the membrane is –90 mV relative to the outside. (b) The mem- brane is selectively permeable to Na+ , and the inner chamber contains a tenfold lower concentration of Na+ than the outer cham- ber; at equilibrium, the inside of the mem- brane is +62 mV relative to the outside. W H AT I F ? Consider the effect of adding potassium or chloride channels to the mem- brane in (b). How would the membrane poten- tial be affected in each case?
6. 1066 UNIT SEVEN Animal Form and Function to that of K+ (see Table 48.1). Na+ therefore diffuses into the cell, making the inside of the cell less negative. If we model a membrane in which the only open channels are selectively permeable to Na+ , we find that a tenfold higher concentration of Na+ in the outer chamber results in an equilibrium poten- tial (ENa) of +62 mV (Figure 48.7b). In an actual neuron, the resting potential (-60 to -80 mV) is much closer to EK than to ENa because there are many open potassium channels but only a small number of open sodium channels. Because neither K+ nor Na+ is at equilibrium in a rest- ing neuron, there is a net flow of each ion (a current) across the membrane. The resting potential remains steady, which means that the K+ and Na+ currents are equal and opposite. Ion concentrations on either side of the membrane also re- main steady. Why? The resting potential arises from the net movement of far fewer ions than would be required to alter the concentration gradients. Under conditions that allow Na+ to cross the membrane more readily, the membrane potential will move toward ENa and away from EK. As you'll see in the next section, this is precisely what happens during the generation of a nerve impulse. C O N C E P T 48.3 Action potentials are the signals conducted by axons When a neuron responds to a stimulus, such as the scent of fish detected by a hunting cone snail, the membrane poten- tial changes. Using the technique of intracellular recording, researchers can record these changes as a function of time (Figure 48.8). Changes in the membrane potential occur because neurons contain gated ion channels, ion channels that open or close in response to stimuli. The opening or closing of gated ion channels alters the membrane's perme- ability to particular ions, which in turn alters the membrane potential. C O N C E P T C H E C K 4 8 . 2 1. Under what circumstances could ions flow through an ion channel from a region of lower ion concentration to a region of higher ion concentration? 2. W H AT I F ? Suppose a cell's membrane potential shifts from -70 mV to -50 mV. What changes in the cell's per- meability to K+ or Na+ could cause such a shift? 3. M A K E C O N N E C T I O N S Review Figure 7.10, which illus- trates the diffusion of dye molecules across a membrane. Could diffusion eliminate the concentration gradient of a dye that has a net charge? Explain. For suggested answers, see Appendix A. Gate closed: No ions flow across membrane. Gate open: Ions flow through channel. Change in membrane potential (voltage) Ions Ion channel ▲ Figure 48.9 Voltage-gated ion channel. A change in the mem- brane potential in one direction (indicated by the right-pointing arrow) opens the voltage-gated channel. The opposite change (left-pointing arrow) closes the channel. Research Method▼ Figure 48.8 Application Electrophysiologists use intracellular recording to mea- sure the membrane potential of neurons and other cells. Technique A microelectrode is made from a glass capillary tube filled with an electrically conductive salt solution. One end of the tube tapers to an extremely fine tip (diameter 6 1 μm). While looking through a microscope, the experimenter uses a micropositioner to insert the tip of the microelectrode into a cell. A voltage recorder (usually an oscil- loscope or a computer-based system) measures the voltage between the microelectrode tip inside the cell and a reference electrode placed in the solution outside the cell. Intracellular Recording Microelectrode Reference electrode Voltage recorder Hyperpolarization and Depolarization When gated ion channels are stimulated to open, ions flow across the membrane, changing the membrane potential (Figure 48.9). For example, opening gated potassium chan- nels in a resting neuron increases the membrane's perme- ability to K+ . Net diffusion of K+ out of the neuron increases, shifting the membrane potential toward EK (-90 mV at 37°C). This increase in the magnitude of the membrane potential, called a hyperpolarization, makes the inside of the membrane more negative (Figure 48.10a). In a resting neuron, hyperpolarization results from any stimulus that increases the outflow of positive ions or the inflow of nega- tive ions.
7. CHAPTER 48 Neurons, Synapses, and Signaling 1067 therefore spread along axons, making them well suited for transmitting a signal over long distances. Action potentials arise because some of the ion channels in neurons are voltage-gated ion channels, opening or clos- ing when the membrane potential passes a particular level (see Figure 48.9). If a depolarization opens voltage-gated so- dium channels, the resulting flow of Na+ into the neuron re- sults in further depolarization. Because the sodium channels are voltage gated, the increased depolarization causes more sodium channels to open, leading to an even greater flow of current. The result is a process of positive feedback that triggers a very rapid opening of many voltage-gated sodium channels and the marked temporary change in membrane potential that defines an action potential (Figure 48.10c). Action potentials occur whenever a depolarization increases the membrane voltage to a particular value, called the threshold. For many mammalian neurons, the threshold is a membrane potential of about -55 mV. Once initiated, the action potential has a magnitude that is inde- pendent of the strength of the triggering stimulus. Because action potentials either occur fully or do not occur at all, they represent an all-or-none response to stimuli. This all- or-none property reflects the fact that depolarization opens voltage-gated sodium channels, causing further depolariza- tion. The positive-feedback loop of channel opening and depolarization triggers an action potential whenever the membrane potential reaches threshold. Although opening potassium channels in a resting neuron causes hyperpolarization, opening some other types of ion channels has an opposite effect, making the inside of the membrane less negative (Figure 48.10b). A reduction in the magnitude of the membrane potential is a depolarization. In neurons, depolarization often involves gated sodium channels. If a stimulus causes gated sodium channels to open, the mem- brane's permeability to Na+ increases. Na+ diffuses into the cell along its concentration gradient, causing a depolarization as the membrane potential shifts toward ENa (+62 mV at 37°C). Graded Potentials and Action Potentials Sometimes, the response to hyperpolarization or depolar- ization is simply a shift in the membrane potential. This shift, called a graded potential, has a magnitude that varies with the strength of the stimulus: A larger stimulus causes a greater change in the membrane potential (see Figure 48.10a and b). Graded potentials induce a small electrical current that leaks out of the neuron as it flows along the membrane. Graded potentials thus decay with time and with distance from their source. If a depolarization shifts the membrane potential suffi- ciently, the result is a massive change in membrane voltage called an action potential. Unlike graded potentials, action potentials have a constant magnitude and can regenerate in adjacent regions of the membrane. Action potentials can Strong depolarizing stimulus Membranepotential(mV) Time (msec) –100 0 1 2 3 4 +50 –50 0 Stimulus Threshold Threshold Threshold Resting potential Hyperpolarizations Membranepotential(mV) Time (msec) –100 0 1 2 3 4 +50 –50 0 Stimulus Membranepotential(mV) Time (msec) –100 0 1 2 3 4 +50 –50 0 5 65 5 Action potential Resting potential Depolarizations Resting potential (a) Graded hyperpolarizations produced by two stimuli that increase membrane permeability to K+.The larger stimulus produces a larger hyperpolarization. (b) Graded depolarizations produced by two stimuli that increase membrane permeability to Na+.The larger stimulus produces a larger depolarization. (c) Action potential triggered by a depolarization that reaches the threshold. ▲ Figure 48.10 Graded potentials and an action potential in a neuron. D R AW I T Redraw the graph in (c), extending the y-axis. Then label the positions of EK and ENa.
8. 1068 UNIT SEVEN Animal Form and Function movement through voltage-gated sodium and potassium channels (Figure 48.11). Depolarization opens both types of channels, but they respond independently and sequen- tially. Sodium channels open first, initiating the action po- tential. As the action potential proceeds, sodium channels become inactivated: A loop of the channel protein moves, blocking ion flow through the opening. Sodium channels remain inactivated until after the membrane returns to the resting potential and the channels close. In contrast, potas- sium channels open more slowly than sodium channels, but remain open and functional until the end of the action potential. The discovery of how action potentials are generated re- sulted from the work of British scientists Andrew Huxley and Alan Hodgkin in the 1940s and 1950s. Because no techniques were available for studying electrical events in small cells, they took electrical recordings from the giant neurons of the squid. Their experiments led to the model presented in the next section, which earned them a Nobel Prize. Generation of Action Potentials: A Closer Look The characteristic shape of the graph of an action potential reflects changes in membrane potential resulting from ion Rising phase of the action potential Time Membranepotential (mV) +50 0 –50 –100 Action potential Threshold Resting potential 1 3 1 2 3 + + – – + + – – + + – – + + – – Depolarization opens most sodium channels, while the potassium channels remain closed. Na+ influx makes the inside of the membrane positive with respect to the outside. Falling phase of the action potential4 – – + + – – + + – – + + – – + + Most sodium channels become inactivated, blocking Na+ inflow. Most potassium channels open, permitting K+ outflow, which makes the inside of the cell negative again. Undershoot5 – – + + – – + + – – + + – – + + The sodium channels close, but some potassium channels are still open. As these potassium channels close and the sodium channels become unblocked (though still closed), the membrane returns to its resting state. Resting state1 – – + + – + – + – + – – + + – – + + – – + + Potassium channel Sodium channel OUTSIDE OF CELL INSIDE OF CELL Inactivation loop Depolarization2 – – + + – – + + – – + + – – + + A stimulus opens some sodium channels. Na+ inflow through those channels depolarizes the membrane. If the depolarization reaches the threshold, it triggers an action potential. 5 4 – + – + – + – – + The gated Na+ and K+ channels are closed. Ungated channels (not shown) maintain the resting potential. Key K+ Na+ ▲ Figure 48.11 The role of voltage-gated ion channels in the generation of an action potential. The circled numbers on the graph in the center and the colors of the action potential phases correspond to the five diagrams showing voltage-gated sodium and potassium channels in a neuron's plasma membrane. (Ungated ion channels are not illustrated.) Visit the Study Area in MasteringBiology for the BioFlix® 3-D Animation on How Neurons Work. A N I M AT I O N
9. CHAPTER 48 Neurons, Synapses, and Signaling 1069 action potential is an all-or-none event, the magnitude and duration of the action potential are the same at each position along the axon. The net result is the movement of a nerve impulse from the cell body to the synaptic terminals, much like the cascade of events triggered by knocking over the first domino in a line. To understand further how voltage-gated channels shape the action potential, consider the process as a series of stages, as depicted in Figure 48.11. 1 When the membrane of the axon is at the resting potential, most voltage-gated sodium channels are closed. Some potassium channels are open, but most voltage-gated potassium channels are closed. 2 When a stimulus depolarizes the membrane, some gated sodium channels open, allowing more Na+ to diffuse into the cell. The Na+ inflow causes further depolarization, which opens still more gated sodium channels, allowing even more Na+ to diffuse into the cell. 3 Once the threshold is crossed, the positive-feedback cycle rapidly brings the membrane potential close to ENa. This stage of the action potential is called the rising phase. 4 Two events prevent the mem- brane potential from actually reaching ENa: Voltage-gated sodium channels inactivate soon after opening, halting Na+ inflow; and most voltage-gated potassium channels open, causing a rapid outflow of K+ . Both events quickly bring the membrane potential back toward EK. This stage is called the falling phase. 5 In the final phase of an action potential, called the undershoot, the membrane's permeability to K+ is higher than at rest, so the membrane potential is closer to EK than it is at the resting potential. The gated potassium channels eventually close, and the membrane potential re- turns to the resting potential. The sodium channels remain inactivated during the falling phase and the early part of the undershoot. As a re- sult, if a second depolarizing stimulus occurs during this period, it will be unable to trigger an action potential. The "downtime" when a second action potential cannot be initi- ated is called the refractory period. One consequence of the refractory period is to limit the maximum frequency at which action potentials can be generated. As we will discuss shortly, the refractory period also ensures that all signals in an axon travel in one direction, from the cell body to the axon terminals. Note that the refractory period is due to the inactivation of sodium channels, not to a change in the ion gradients across the plasma membrane. The flow of charged par- ticles during an action potential involves far too few ions to change the concentration on either side of the membrane significantly. Conduction of Action Potentials Having described the events of a single action potential, we'll explore next how a series of action potentials moves a signal along an axon. At the site where an action potential is initi- ated (usually the axon hillock), Na+ inflow during the rising phase creates an electrical current that depolarizes the neigh- boring region of the axon membrane (Figure 48.12). The depolarization is large enough to reach threshold, causing an action potential in the neighboring region. This process is re- peated many times along the length of the axon. Because an – – – – Na+ Action potential Plasma membrane Action potential Action potential + + + + + + + + + + – – + + – – + + + + + + Na+ + + – – + + – – + + Na+ K+ K+ + + + + – – – – – – – – – – – – + – – + + – – – – – – – – + + – – + + + + + + + + + + + + + + – – – – – – – – – – – – + K+ K+ An action potential is generated as Na+ flows inward across the membrane at one location. The depolarization of the action potential spreads to the neighboring region of the membrane, reinitiating the action potential there. To the left of this region, the membrane is repolarizing as K+ flows outward. The depolarization-repolarization process is repeated in the next region of the membrane. In this way, local currents of ions across the plasma membrane cause the action potential to be propagated along the length of the axon. Axon Cytosol ▲ Figure 48.12 Conduction of an action potential. This figure shows events at three successive times as an action potential passes from left to right. At each point along the axon, voltage-gated ion chan- nels go through the sequence of changes shown in Figure 48.11. Mem- brane colors correspond to the action potential phases in Figure 48.11. D R AW I T For the axon segment shown, consider a point at the left end, a point in the middle, and a point at the right end. Draw a graph for each point showing the change in membrane potential over time at that point as a single nerve impulse moves from left to right across the segment.
10. 1070 UNIT SEVEN Animal Form and Function Evolutionary Adaptations of Axon Structure E VO L U T I O N The rate at which the axons within nerves conduct action potentials governs how rapidly an animal can react to danger or opportunity. As a consequence, nat- ural selection often results in anatomical adaptations that increase conduction speed. One such adaptation is a wider axon. Axon width matters because resistance to electrical current flow is inversely proportional to the cross-sectional area of a conductor (such as a wire or an axon). In the same way that a wide hose offers less resistance to the flow of water than does a narrow hose, a wide axon provides less resistance to the current associated with an action potential than does a narrow axon. In invertebrates, conduction speed varies from several centimeters per second in very narrow axons to approxi- mately 30 m/sec in the giant axons of some arthropods and molluscs. These giant axons (up to 1 mm wide) function in rapid behavioral responses, such as the muscle contraction that propels a hunting squid toward its prey. Vertebrate axons have narrow diameters but can still conduct action potentials at high speed. How is this pos- sible? The evolutionary adaptation that enables fast conduc- tion in vertebrate axons is electrical insulation, analogous to the plastic insulation that encases many electrical wires. Insulation causes the depolarizing current associated with an action potential to travel farther along the axon interior, bringing more distant regions to the threshold sooner. The electrical insulation that surrounds vertebrate axons is called a myelin sheath (Figure 48.13). Myelin sheaths are produced by two types of glia: oligodendrocytes in the CNS and Schwann cells in the PNS. During development, these specialized glia wrap axons in many layers of membrane. The membranes forming these layers are mostly lipid, which is a poor conductor of electrical current and thus a good insulator. An action potential that starts at the axon hillock moves along the axon only toward the synaptic terminals. Why? Immediately behind the traveling zone of depolarization caused by Na+ inflow is a zone of repolarization caused by K+ outflow. In the repolarized zone, the sodium channels remain inactivated. Consequently, the inward current that depolarizes the axon membrane ahead of the action poten- tial cannot produce another action potential behind it. This prevents action potentials from traveling back toward the cell body. For most neurons, the interval between the onset of an action potential and the beginning of the undershoot is only 1–2 milliseconds (msec). Because action potentials are so brief, a neuron can produce them as often as hundreds per second. Furthermore, the rate at which action potentials are produced conveys information about the strength of the input signal. In hearing, for example, louder sounds result in more frequent action potentials in neurons connecting the ear to the brain. Similarly, increased frequency of action potentials in a neuron that stimulates skeletal muscle tissue will increase the tension in the contracting muscle. Differ- ences in the number of action potentials in a given time are in fact the only variable in how information is encoded and transmitted along an axon. Gated ion channels and action potentials have a central role in nervous system activity. As a consequence, mutations in genes that encode ion channel proteins can cause disor- ders affecting the nerves or brain—or the muscles or heart, depending largely on where in the body the gene for the ion channel protein is expressed. For example, mutations affect- ing voltage-gated sodium channels in skeletal muscle cells can cause myotonia, a periodic spasming of those muscles. Mutations affecting sodium channels in the brain can cause epilepsy, in which groups of nerve cells fire simultaneously and excessively, producing seizures. Axon Layers of myelin Node of Ranvier Axon Schwann cell Schwann cell Nucleus of Schwann cellMyelin sheath Nodes of Ranvier 0.1 μm ▲ Figure 48.13 Schwann cells and the myelin sheath. In the PNS, glia called Schwann cells wrap themselves around axons, forming layers of myelin. Gaps between adjacent Schwann cells are called nodes of Ranvier. The TEM shows a cross section through a myelinated axon.
11. CHAPTER 48 Neurons, Synapses, and Signaling 1071 – Myelin sheath Axon Depolarized region (node of Ranvier) + + –– –– + + + + – – – + + + +– – Cell body Schwann cell C O N C E P T 48.4 Neurons communicate with other cells at synapses In most cases, action potentials are not transmitted from neurons to other cells. However, information is transmitted, and this transmission occurs at synaptic terminals, such as those shown in Figure 48.15. Some synapses, called electri- cal synapses, contain gap junctions (see Figure 6.30), which do allow electrical current to flow directly from one neuron to another. In both vertebrates and invertebrates, electrical synapses synchronize the activity of neurons responsible for certain rapid, unvarying behaviors. For example, electri- cal synapses associated with the giant axons of squids and lobsters facilitate swift escapes from danger. There are also many electrical synapses in the vertebrate brain. The majority of synapses are chemical synapses, which involve the release of a chemical neurotransmitter by the presynaptic neuron. At each terminal, the presynaptic neuron synthesizes the neurotransmitter and packages it in multiple membrane-enclosed compartments called synaptic vesicles. The arrival of an action potential at a synaptic terminal depolarizes the plasma membrane, open- ing voltage-gated channels that allow Ca2+ to diffuse into ▶ Figure 48.14 Saltatory conduction. In a myelinated axon, the depolarizing cur- rent during an action potential at one node of Ranvier spreads along the interior of the axon to the next node (blue arrows), where voltage-gated sodium channels enable reini- tiation. Thus, the action potential appears to jump from node to node as it travels along the axon (red arrows). 5μmSynaptic terminals of pre- synaptic neurons Postsynaptic neuron ▲ Figure 48.15 Synaptic terminals on the cell body of a post- synaptic neuron (colorized SEM). In myelinated axons, voltage-gated sodium channels are restricted to gaps in the myelin sheath called nodes of Ranvier (see Figure 48.13). Furthermore, the extracellu- lar fluid is in contact with the axon membrane only at the nodes. As a result, action potentials are not generated in the regions between the nodes. Rather, the inward current produced during the rising phase of the action potential at a node travels within the axon all the way to the next node. There, the current depolarizes the membrane and regener- ates the action potential (Figure 48.14). Action potentials propagate more rapidly in myelinated axons because the time-consuming process of opening and closing of ion channels occurs at only a limited number of positions along the axon. This mechanism for propagating action potentials is called saltatory conduction (from the Latin saltare, to leap) because the action potential appears to jump along the axon from node to node. The major selective advantage of myelination is its space efficiency. A myelinated axon 20 μm in diameter has a con- duction speed faster than that of a squid giant axon with a diameter 40 times greater. Consequently, more than 2,000 of those myelinated axons can be packed into the space oc- cupied by just one giant axon. For any axon, myelinated or not, the conduction of an action potential to the end of the axon sets the stage for the next step in neuronal signaling—the transfer of information to another cell. This information handoff occurs at synapses, our next topic. C O N C E P T C H E C K 4 8 . 3 1. How do action potentials and graded potentials differ? 2. In multiple sclerosis (from the Greek skleros, hard), a per- son's myelin sheaths harden and deteriorate. How would this affect nervous system function? 3. How do both negative and positive feedback contribute to the changes in membrane potential during an action potential? 4. W H AT I F ? Suppose a mutation caused gated sodium channels to remain inactivated longer after an action potential. How would this affect the frequency at which action potentials could be generated? Explain. For suggested answers, see Appendix A.
12. 1072 UNIT SEVEN Animal Form and Function the terminal (Figure 48.16). The resulting rise in Ca2+ concentration in the terminal causes some of the synaptic vesicles to fuse with the terminal membrane, releasing the neurotransmitter. Once released, the neurotransmitter diffuses across the synaptic cleft, the gap that separates the presynaptic neuron from the postsynaptic cell. Diffusion time is very short be- cause the gap is less than 50 nm across. Upon reaching the postsynaptic membrane, the neurotransmitter binds to and activates a specific receptor in the membrane. Information transfer is much more readily modified at chemical synapses than at electrical synapses. A variety of factors can affect the amount of neurotransmitter that is released or the responsiveness of the postsynaptic cell. Such modifications underlie an animal's ability to alter its The depolarization opens voltage-gated channels, triggering an influx of Ca2+. Postsynaptic membrane Na+ K+ Synaptic vesicle containing neurotransmitter Presynaptic membrane Axon Synaptic cleft Voltage-gated Ca2+ channel Ca2+ Ligand-gated ion channels Postsynaptic cellPresynaptic cell 1 An action potential arrives, depolarizing the presynaptic membrane. 2 The elevated Ca2+ concentration causes synaptic vesicles to fuse with the presynaptic membrane, releasing neurotransmitter into the synaptic cleft. 3 The neurotransmitter binds to ligand-gated ion channels in the postsynaptic membrane. In this example, binding triggers opening, allowing Na+ and K+ to diffuse through. 4 ▲ Figure 48.16 A chemical synapse. This figure illustrates the sequence of events that trans- mits a signal across a chemical synapse. In response to binding of neurotransmitter, ligand-gated ion channels in the postsynaptic membrane open (as shown here) or, less commonly, close. Synap- tic transmission ends when the neurotransmitter diffuses out of the synaptic cleft, is taken up by the synaptic terminal or by another cell, or is degraded by an enzyme. W H AT I F ? If all the Ca2+ in the fluid surrounding a neuron were removed, how would this affect the transmission of information within and between neurons? Visit the Study Area in MasteringBiology for the BioFlix® 3-D Animation on How Synapses Work. A N I M AT I O N behavior in response to change and form the basis for learn- ing and memory (as you will read in Chapter 49). Generation of Postsynaptic Potentials At many chemical synapses, the receptor protein that binds and responds to neurotransmitters is a ligand-gated ion channel, often called an ionotropic receptor. These recep- tors are clustered in the membrane of the postsynaptic cell, directly opposite the synaptic terminal. Binding of the neurotransmitter (the receptor's ligand) to a particular part of the receptor opens the channel and allows specific ions to diffuse across the postsynaptic membrane. The result is a postsynaptic potential, a graded potential in the postsyn- aptic cell. At some synapses, the ligand-gated ion channel is per- meable to both K+ and Na+ (see Figure 48.16). When this channel opens, the membrane potential depolarizes toward a value roughly midway between EK and ENa. Because such a depolarization brings the membrane potential
13. CHAPTER 48 Neurons, Synapses, and Signaling 1073 toward threshold, it is called an excitatory postsynaptic potential (EPSP). At other synapses, the ligand-gated ion channel is selec- tively permeable for only K+ or Cl- . When such a channel opens, the postsynaptic membrane hyperpolarizes. A hyper- polarization produced in this manner is an inhibitory postsynaptic potential (IPSP) because it moves the mem- brane potential further from threshold. Summation of Postsynaptic Potentials The cell body and dendrites of a postsynaptic neuron may receive inputs from chemical synapses formed with hundreds or even thousands of synaptic terminals (see Figure 48.15). Often, some of these are excitatory and others inhibitory. The magnitude of the postsynaptic potential at any one synapse varies with a number of factors, including the amount of neurotransmitter released by the presynaptic neuron. As a graded potential, a postsynaptic potential be- comes smaller with distance from the synapse. Therefore, by the time a single EPSP reaches the axon hillock, it is usually too small to trigger an action potential (Figure 48.17a). On some occasions, two EPSPs occur at a single synapse in such rapid succession that the postsynaptic neuron's membrane potential has not returned to the resting po- tential before the arrival of the second EPSP. When that happens, the EPSPs add together, an effect called temporal summation (Figure 48.17b). Moreover, EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron can also add together, an effect called spatial summation (Figure 48.17c). Through spatial and temporal summation, several EPSPs can combine to depo- larize the membrane at the axon hillock to threshold, caus- ing the postsynaptic neuron to produce an action potential. Summation applies as well to IPSPs: Two or more IPSPs occurring nearly simultaneously at synapses in the same region or in rapid succession at the same synapse have a larger effect than a single IPSP. Through summation, an IPSP can also counter the effect of an EPSP (Figure 48.17d). The interplay between multiple excitatory and inhibitory inputs is the essence of integration in the nervous system. The axon hillock is the neuron's integrating center, the region where the membrane potential at any instant repre- sents the summed effect of all EPSPs and IPSPs. Whenever the membrane potential at the axon hillock reaches thresh- old, an action potential is generated and travels along the axon to its synaptic terminals. After the refractory period, the neuron may produce another action potential, provided the membrane potential at the axon hillock once again reaches threshold. Modulated Signaling at Synapses So far, we have focused on synapses where a neurotrans- mitter binds directly to an ion channel, causing the chan- nel to open. However, there are also synapses in which the receptor for the neurotransmitter is not part of an ion channel. At these synapses, the neurotransmitter binds Resting potential Action potential Threshold of axon of postsynaptic neuron Postsynaptic neuron Terminal branch of presynaptic neuron E1 (a) (b) Temporal summation (c) Spatial summation (d) E1 E1 E1E1 E1 + E2 I E1 + I Membranepotential(mV) –70 0 E1 E1 E1E1 IIII E2 E2E2E2 Axon hillock Action potential Spatial summation of EPSP and IPSP Subthreshold, no summation ▲ Figure 48.17 Summation of postsynaptic potentials. These graphs trace changes in the membrane potential at a postsynaptic neuron's axon hillock. The arrows indicate times when post- synaptic potentials occur at two excitatory synapses (E1 and E2, green in the diagrams above the graphs) and at one inhibitory synapse (I, red). Like most EPSPs, those produced at E1 or E2 do not reach the threshold at the axon hillock without summation.
14. 1074 UNIT SEVEN Animal Form and Function Acetylcholine Acetylcholine is vital for nervous system functions that include muscle stimulation, memory formation, and learn- ing. In vertebrates, there are two major classes of acetyl- choline receptor. One is a ligand-gated ion channel, which functions at the vertebrate neuromuscular junction, the site where a motor neuron forms a synapse with a skeletal muscle cell. When acetylcholine released by motor neu- rons binds this receptor, the ion channel opens, producing an EPSP. This excitatory activity is soon terminated by acetylcholinesterase, an enzyme in the synaptic cleft that hydrolyzes the neurotransmitter. The acetylcholine receptor active at the neuromuscular junction is also found elsewhere in the PNS, as well as in the CNS. There this ionotropic receptor can bind nicotine, a chemical found in tobacco and tobacco smoke. Nicotine's effects as a physiological and psychological stimulant result from its binding to this receptor. A metabotropic acetylcholine receptor is found at loca- tions that include the vertebrate CNS and heart. In heart muscle, acetylcholine released by neurons activates a signal transduction pathway. The G proteins in the pathway in- hibit adenylyl cyclase and open potassium channels in the muscle cell membrane. Both effects reduce the rate at which the heart pumps. Thus, the effect of acetylcholine in heart muscle is inhibitory rather than excitatory. to a metabotropic receptor, so called because the result- ing opening or closing of ion channels depends on one or more metabolic steps. Binding of a neurotransmitter to a metabotropic receptor activates a signal transduction pathway in the postsynaptic cell involving a second mes- senger (see Chapter 11). Compared with the postsynaptic potentials produced by ligand-gated channels, the effects of these second-messenger systems have a slower onset but last longer (minutes or even hours). Second messengers modulate the responsiveness of postsynaptic neurons to inputs in diverse ways, such as by altering the number of open potassium channels. A variety of signal transduction pathways play a role in modulating synaptic transmission. One of the best- studied pathways involves cyclic AMP (cAMP) as a second messenger. For example, when the neurotransmitter nore- pinephrine binds to its metabotropic receptor, the neurotransmitter–receptor complex activates a G protein, which in turn activates adenylyl cyclase, the enzyme that converts ATP to cAMP (see Figure 11.11). Cyclic AMP activates protein kinase A, which phosphorylates specific ion channel proteins in the postsynaptic membrane, caus- ing them to open or close. Because of the amplifying effect of the signal transduction pathway, the binding of a neu- rotransmitter molecule to a metabotropic receptor can open or close many channels. Neurotransmitters Signaling at a synapse brings about a response that depends on both the neurotransmitter released from the presynaptic membrane and the receptor produced at the postsynaptic membrane. A single neurotransmitter may bind specifi- cally to more than a dozen different receptors, including ionotropic and metabotropic types. Indeed, a particular neu- rotransmitter can excite postsynaptic cells expressing one receptor and inhibit postsynaptic cells expressing a different receptor. How is neurotransmitter signaling terminated? Both receptor activation and postsynaptic response cease when neurotransmitter molecules are cleared from the synaptic cleft. The removal of neurotransmitters can occur by simple diffusion or by other mechanisms. For example, some neu- rotransmitters are inactivated by enzymatic hydrolysis (Figure 48.18a). Other neurotransmitters are recaptured into the presynaptic neuron (Figure 48.18b). Once this reuptake occurs, neurotransmitters are repackaged in syn- aptic vesicles or transferred to glia for metabolism or recy- cling to neurons. With these basic properties of neurotransmitters in mind, let's now examine some specific examples, beginning with acetylcholine, a common neurotransmitter in both inverte- brates and vertebrates. Enzymatic breakdown of neurotransmitter in the synaptic cleft(a) PRESYNAPTIC NEURON POSTSYNAPTIC NEURON Neurotransmitter Neurotransmitter receptor Inactivating enzyme Reuptake of neurotransmitter by presynaptic neuron(b) Neurotransmitter Neurotransmitter receptor Neurotransmitter transport channel ▲ Figure 48.18 Two mechanisms of terminating neurotransmission.
15. CHAPTER 48 Neurons, Synapses, and Signaling 1075 junction. In vertebrates, glutamate is the most common neurotransmitter in the CNS. Synapses at which glutamate is the neurotransmitter have a key role in the formation of long-term memory (as we will discuss in Chapter 49). The amino acid gamma-aminobutyric acid (GABA) is the neurotransmitter at most inhibitory synapses in the brain. Binding of GABA to receptors in postsynaptic cells increases membrane permeability to Cl- , resulting in an IPSP. The widely prescribed drug diazepam (Valium) re- duces anxiety through binding to a site on a GABA receptor. A third amino acid, glycine, acts at inhibitory synapses in parts of the CNS that lie outside of the brain. There, glycine binds to an ionotropic receptor that is inhibited by strych- nine, a chemical often used as a rat poison. Biogenic Amines The neurotransmitters grouped as biogenic amines are synthesized from amino acids and include norepinephrine, which is made from tyrosine. Norepinephrine is an excitatory neurotransmitter in the autonomic nervous system, a branch of the PNS. Outside the nervous system, norepinephrine has distinct but related functions as a hormone, as does the chem- ically similar biogenic amine epinephrine (see Chapter 45). The biogenic amines dopamine, made from tyrosine, and serotonin, made from tryptophan, are released at many sites in the brain and affect sleep, mood, attention, and learning. Some psychoactive drugs, including LSD and mescaline, ap- parently produce their hallucinatory effects by binding to brain receptors for these neurotransmitters. Biogenic amines have a central role in a number of ner- vous system disorders and treatments (see Chapter 49). The degenerative illness Parkinson's disease is associated with a lack of dopamine in the brain. In addition, depres- sion is often treated with drugs that increase the brain concentrations of biogenic amines. Prozac, for instance, enhances the effect of serotonin by inhibiting its reuptake after release. Neuropeptides Several neuropeptides, relatively short chains of amino acids, serve as neurotransmitters that operate via metabotropic re- ceptors. Such peptides are typically produced by cleavage of much larger protein precursors. The neuropeptide substance P is a key excitatory neurotransmitter that mediates our percep- tion of pain, while other neuropeptides, called endorphins, function as natural analgesics, decreasing pain perception. Endorphins are produced in the brain during times of physical or emotional stress, such as childbirth. In addi- tion to relieving pain, they reduce urine output, decrease respiration, and produce euphoria, as well as other emo- tional effects. Because opiates (drugs such as morphine and heroin) bind to the same receptor proteins as endorphins, opiates mimic endorphins and produce many of the same A number of toxins disrupt neurotransmission by ace- tylcholine. For example, the nerve gas sarin inhibits acetyl- cholinesterase, causing a buildup of acetylcholine to levels that trigger paralysis and typically death. In contrast, certain bacteria produce a toxin that inhibits presynaptic release of acetylcholine. This toxin causes a rare but often fatal form of food poisoning called botulism. Untreated botulism is typically fatal because muscles required for breathing fail to contract when acetylcholine release is blocked. Today, injections of the botulinum toxin, known by the trade name Botox, are used cosmetically to minimize wrinkles around the eyes or mouth by blocking transmission at synapses that control particular facial muscles. Although acetylcholine has many roles, it is just one of more than 100 known neurotransmitters. As shown by the examples in Table 48.2, the rest fall into four classes: amino acids, biogenic amines, neuropeptides, and gases. Amino Acids Glutamate is one of several amino acids that can act as a neurotransmitter. In invertebrates, glutamate, rather than acetylcholine, is the neurotransmitter at the neuromuscular Neurotransmitter Structure Acetylcholine Amino Acids Glutamate Biogenic Amines Neuropeptides Gases Table 48.2 Major Neurotransmitters N O Tyr Gly Gly Phe Met Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met CH2 CH2 C CH N H HO NH2 CH2 CH2 HO HO NH2 CH2 CH OH HO HO NH2 H2 N CH2 COOH H2 N CH2 CH2 COOHCH2 H2 N CH COOH CH2 CH2 COOH H3 C C O O CH2 CH2 CH3 CH3 CH3 N+
16. 1076 UNIT SEVEN Animal Form and Function physiological effects (see Figure 2.16). In the Scientific Skills Exercise, you can interpret data from an experiment de- signed to search for opiate receptors in the brain. Gases Some vertebrate neurons release dissolved gases as neuro- transmitters. In human males, for example, certain neurons release nitric oxide (NO) into the erectile tissue of the penis during sexual arousal. The resulting relaxation of smooth muscle in the blood vessel walls of the spongy erectile tissue allows the tissue to fill with blood, producing an erection. The erectile dysfunction drug Viagra works by inhibiting an enzyme that terminates the action of NO. Unlike most neurotransmitters, NO is not stored in cyto- plasmic vesicles but is instead synthesized on demand. NO diffuses into neighboring target cells, produces a change, and is broken down—all within a few seconds. In many of its targets, including smooth muscle cells, NO works like many hormones, stimulating an enzyme to synthesize a second messenger that directly affects cellular metabolism. Although inhaling the gas carbon monoxide (CO) can be deadly, the vertebrate body uses the enzyme heme oxygenase to produce small amounts of CO, some of which acts as a neurotransmitter. In the brain, CO regulates the release of hypothalamic hormones. In the PNS, it acts as an inhibitory neurotransmitter that hyperpolarizes the plasma membrane of intestinal smooth muscle cells. In the next chapter, we'll consider how the cellular and biochemical mechanisms we have discussed contribute to nervous system function on the system level. S C I E N T I F I C S K I L L S E X E R C I S E Does the Brain Have Specific Protein Receptors for Opiates? A team of researchers were looking for opiate receptors in the mamma- lian brain. Knowing that the drug naloxone blocks the analgesic effect of opiates, they hypothesized that naloxone acts by binding tightly to brain opiate receptors without activating them. In this exercise, you will interpret the results of an experiment that the researchers conducted to test their hypothesis. How the Experiment Was Done The researchers added radioac- tive naloxone to a protein mixture prepared from rodent brains. If the mixture contained opiate receptors or other proteins that could bind naloxone, the radioactivity would stably associate with the mixture. To determine whether the binding was due to specific opiate receptors, they tested other drugs, opiate and non-opiate, for their ability to block naloxone binding. Radioactive naloxone Drug Radioactive naloxone and a test drug are incubated with a protein mixture. 1 Proteins are trapped on a filter. Bound naloxone is detected by measuring radioactivity. 2 Interpreting Data Values Expressed in Scientific Notation Data from the Experiment Drug Opiate Lowest Concentration That Blocked Naloxone Binding Yes * -9 M Yes * -8 M Yes * -9 M -4 M -4 M -4 M Interpret the Data 1. The data above are expressed in scientific notation: a numerical factor times a power of 10. Remember that a negative power of 10 means a number less than 1. For example, 10-1 M (molar) can also be written as 0.1 M. Write the concentrations in the table above for morphine and atropine in this alternative format. 2. Compare the concentrations listed in the table for methadone and phenobarbital. Which concentration is higher? By how much? 3. Would phenobarbital, atropine, or serotonin have blocked naloxone binding at a concentration of 10-5 M? Explain why or why not. 4. Which drugs blocked naloxone binding in this experiment? What do these results indicate about the brain receptors for naloxone? 5. If researchers instead used tissue from intestinal muscles rather than brains, they found no naloxone binding. What does that suggest about opiate receptors in mammalian muscle? A version of this Scientific Skills Exercise can be assigned in MasteringBiology. Data from C. B. Pert and S. H. Snyder, Opiate receptor: demonstration in nervous tis- sue, Science 179:1011–1014 (1973). C O N C E P T C H E C K 4 8 . 4 1. How is it possible for a particular neurotransmitter to pro- duce opposite effects in different tissues? 2. Organophosphate pesticides work by inhibiting ace- tylcholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine. Explain how these toxins would affect EPSPs produced by acetylcholine. 3. M A K E C O N N E C T I O N S Name one or more membrane activities that occur both in fertilization of an egg and in neurotransmission across a synapse (see Figure 47.3). For suggested answers, see Appendix A.
17. CHAPTER 48 Neurons, Synapses, and Signaling 1077 negative membrane potential is restored by the inactivation of sodium channels and by the opening of many voltage-gated potassium channels, which increases K+ outflow. A refractory period follows, corresponding to the interval when the sodium channels are inactivated. SUMMARY OF KEY CONCEPTS C O N C E P T 48.1 Neuron structure and organization reflect function in information transfer (pp. 1062–1064) Most neurons have branched dendrites that receive signals from other neurons and an axon that transmits signals to other cells at synapses. Neurons rely on glia for functions that include nourishment, insulation, and regulation. Chapter Review48 CHAPTER 48 Neurons, Synapses, and Signaling 1077 Dendrites Axon hillock Axon SynapseSignal direction Presynaptic cell Postsynaptic cell Cell body A central nervous system (CNS) and a peripheral nervous system (PNS) process information in three stages: sensory input, integration, and motor output to effector cells. ? How would severing an axon affect the flow of information in a neuron? C O N C E P T 48.2 Ion pumps and ion channels establish the resting potential of a neuron (pp. 1064–1066) Ionic gradients generate a voltage difference, or membrane po- tential, across the plasma membrane of cells. The concentration of Na+ is higher outside than inside; the reverse is true for K+ . In resting neurons, the plasma membrane has many open potas- sium channels but few open sodium channels. Diffusion of ions, principally K+ , through channels generates a resting potential, with the inside more negative than the outside. ? Suppose you placed an isolated neuron in a solution similar to extracellular fluid and later transferred the neuron to a solution lack- ing any sodium ions. What change would you expect in the resting potential? C O N C E P T 48.3 Action potentials are the signals conducted by axons (pp. 1066–1071) Neurons have gated ion channels that open or close in response to stimuli, leading to changes in the membrane potential. An increase in the magnitude of the membrane potential is a hyperpolarization; a decrease is a depolarization. Changes in membrane potential that vary continuously with the strength of a stimulus are known as graded potentials. An action potential is a brief, all-or-none depolarization of a neuron's plasma membrane. When a graded depolarization brings the membrane potential to threshold, many voltage- gated ion channels open, triggering an inflow of Na+ that rapidly brings the membrane potential to a positive value. A Time (msec) Membranepotential(mV) +50 0 –50 –100 0 1 2 3 4 5 6 Threshold (–55) Resting potential Depolarization Undershoot Rising phase Falling phase Action potential –70 A nerve impulse travels from the axon hillock to the synaptic terminals by propagating a series of action potentials along the axon. The speed of conduction increases with the diameter of the axon and, in many vertebrate axons, with myelination. Ac- tion potentials in axons insulated by myelination appear to jump from one node of Ranvier to the next, a process called saltatory conduction. I N T E R P R E T T H E DATA Assuming a refractory period equal in length to the action potential (see graph above), what is the maximum frequency per unit time at which a neuron could fire action potentials? C O N C E P T 48.4 Neurons communicate with other cells at synapses (pp. 1071–1076) In an electrical synapse, electrical current flows directly from one cell to another. In a chemical synapse, depolarization causes synaptic vesicles to fuse with the terminal membrane and release neurotransmitter into the synaptic cleft. At many synapses, the neurotransmitter binds to ligand-gated ion channels in the postsynaptic membrane, producing an excitatory or inhibitory postsynaptic potential (EPSP or IPSP). The neurotransmitter then diffuses out of the cleft, is taken up by surrounding cells, or is degraded by enzymes. A single neuron has many synapses on its dendrites and cell body. Temporal and spatial summation of EPSPs and IPSPs at the axon hillock determine whether a neuron generates an action potential. Different receptors for the same neurotransmitter produce dif- ferent effects. Some neurotransmitter receptors activate signal transduction pathways, which can produce long-lasting changes in postsynaptic cells. Major neurotransmitters include acetyl- choline; the amino acids GABA, glutamate, and glycine; biogenic amines; neuropeptides; and gases such as NO. ? Why are many drugs that are used to treat nervous system diseases or to affect brain function targeted to specific receptors rather than particular neurotransmitters?
18. 1078 UNIT SEVEN Animal Form and Function threshold. Using the drawing below as a model, create one or more drawings that illustrate where each action potential would terminate. Electrode Squid axon 10. EVOLUTION CONNECTION An action potential is an all-or-none event. This on/off signal- ing is an evolutionary adaptation of animals that must sense and act in a complex environment. It is possible to imagine a nervous system in which the action potentials are graded, with the amplitude depending on the size of the stimulus. What evolutionary advantage might on/off signaling have over a graded (continuously variable) kind of signaling? 11. SCIENTIFIC INQUIRY From what you know about action potentials and synapses, propose two or three hypotheses for how various anesthetics might block pain. 12. WRITE ABOUT A THEME: ORGANIZATION In a short essay (100–150 words), describe how the structure and electrical properties of vertebrate neurons reflect similari- ties and differences with other animal cells. 13. SYNTHESIZE YOUR KNOWLEDGE The rattlesnake alerts enemies to its presence with a rattle—a set of modified scales at the tip of its tail. Describe the distinct roles of gated ion channels in initiating and moving a signal along the nerve from the snake's head to its tail and then from that nerve to the muscle that shakes the rattle. For selected answers, see Appendix A. TEST YOUR UNDERSTANDING LEVEL 1: KNOWLEDGE/COMPREHENSION 1. What happens when a resting neuron's membrane depolarizes? a. There is a net diffusion of Na+ out of the cell. b. The equilibrium potential for K+ (EK) becomes more positive. c. The neuron's membrane voltage becomes more positive. d. The cell's inside is more negative than the outside. 2. A common feature of action potentials is that they a. cause the membrane to hyperpolarize and then depolarize. b. can undergo temporal and spatial summation. c. are triggered by a depolarization that reaches threshold. d. move at the same speed along all axons. 3. Where are neurotransmitter receptors located? a. the nuclear membrane b. the nodes of Ranvier c. the postsynaptic membrane d. synaptic vesicle membranes LEVEL 2: APPLICATION/ANALYSIS 4. Why are action potentials usually conducted in one direction? a. Ions can flow along the axon in only one direction. b. The brief refractory period prevents reopening of voltage- gated Na+ channels. c. The axon hillock has a higher membrane potential than the terminals of the axon. d. Voltage-gated channels for both Na+ and K+ open in only one direction. 5. Which of the following is the most direct result of depolarizing the presynaptic membrane of an axon terminal? a. Voltage-gated calcium channels in the membrane open. b. Synaptic vesicles fuse with the membrane. c. Ligand-gated channels open, allowing neurotransmitters to enter the synaptic cleft. d. An EPSP or IPSP is generated in the postsynaptic cell. 6. Suppose a particular neurotransmitter causes an IPSP in post- synaptic cell X and an EPSP in postsynaptic cell Y. A likely ex- planation is that a. the threshold value in the postsynaptic membrane is differ- ent for cell X and cell Y. b. the axon of cell X is myelinated, but that of cell Y is not. c. only cell Y produces an enzyme that terminates the activity of the neurotransmitter. d. cells X and Y express different receptor molecules for this particular neurotransmitter. LEVEL 3: SYNTHESIS/EVALUATION 7. W H AT I F ? Ouabain, a plant substance used in some cultures to poison hunting arrows, disables the sodium-potassium pump. What change in the resting potential would you expect to see if you treated a neuron with ouabain? Explain. 8. W H AT I F ? If a drug mimicked the activity of GABA in the CNS, what general effect on behavior might you expect? Explain. 9. D R AW I T Suppose a researcher inserts a pair of electrodes at two different positions along the middle of an axon dis- sected out of a squid. By applying a depolarizing stimulus, the researcher brings the plasma membrane at both positions to Students Go to MasteringBiology for assignments, the eText, and the Study Area with practice tests, animations, and activities. Instructors Go to MasteringBiology for automatically graded tutorials and questions that you can assign to your students, plus Instructor Resources.