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Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000.

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Molecular Cell Biology. 4th edition.

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Section 21.4Neurotransmitters, Synapses, and Impulse Transmission

As noted earlier, synapses are the junctions where neurons pass signals to other neurons, muscle cells, or gland cells. Most nerve-to-nerve signaling and all known nerve-to-muscle and nerve-to-gland signaling rely on chemical synapses at which the presynaptic neuron releases a chemical neurotransmitter that acts on the postsynaptic target cell (see Figure 21-4). In this section we discuss the types of molecules that function as transmitters at chemical synapses, their origin and fate, and their effects on postsynaptic cells. Because the ability of neurotransmitters to induce a response depends on their binding to specific receptors in the postsynaptic membrane, we introduce the major classes of receptors in this section; individual receptors are examined in more detail in the next section. We also briefly discuss electric synapses, which are much rarer, but simpler in function, than chemical synapses.

Many Small Molecules Transmit Impulses at Chemical Synapses

Numerous small molecules synthesized in the cytosol of axon terminals function as neurotransmitters at various chemical synapses. The “classic” neurotransmitters are stored in synaptic vesicles, uniformly sized organelles, 40 – 50 nm in diameter. With the exception of acetylcholine, the classic neurotransmitters depicted in Figure 21-28 are amino acids or derivatives of amino acids. Nucleotides such as ATP (see Figure 2-24) and the corresponding nucleosides, which lack phosphate groups, also function as neurotransmitters. Each neuron generally produces just one type of classic neurotransmitter. Following their exocytosis from synaptic vesicles into the synaptic cleft, neurotransmitters bind to specific receptors on the plasma membrane of a postsynaptic cell, causing a change in its permeability to ions.

Figure 21-28. Structures of several small molecules that function as neurotransmitters.

Figure 21-28

Structures of several small molecules that function as neurotransmitters. Except for acetylcholine, all of these are amino acids (glycine and glutamate) or derived from the indicated amino (more...)

Many neurons secrete neuropeptides, a varied group of signaling molecules that includes endorphins, vasopressin, oxytocin, and gastrin. Neuropeptides are stored in a different type of vesicle than classic neurotransmitters. Exocytosis of both types of transmitter is triggered by a localized rise in cytosolic Ca2+, but neuropeptides are released outside the synaptic zone. The effects of neuropeptide transmitters are very diverse and often long-lived (hours to days). The following discussion deals mainly with the release and actions of the classic neurotransmitters such as those shown in Figure 21-28.

Influx of Ca2+ Triggers Release of Neurotransmitters

The exocytosis of neurotransmitters from synaptic vesicles involves vesicle-targeting and fusion events similar to those that occur at many points in the secretory pathway (Section 17.10). Indeed the same types of proteins — including T-SNARE and V-SNAREs, α, β, and γ SNAP proteins, and NSF — participate in both systems. However, exocytosis of neurotransmitters at chemical synapses differs from other secretory pathways in two critical ways: (a) Secretion is tightly coupled to arrival of the action potential at the axon terminus, and (b) synaptic vesicles are recycled locally after fusion with the plasma membrane, a process that takes less than one minute.

Depolarization of the plasma membrane cannot, by itself, cause synaptic vesicles to fuse with the plasma membrane. In order to trigger vesicle fusion, an action potential must be converted, or transduced, into a chemical signal — namely, a localized rise in the cytosolic Ca2+ concentration. The transducers of the electric signals are voltage-gated Ca2+ channels localized to the region of the plasma membrane adjacent to the synaptic vesicles. The membrane depolarization due to arrival of an action potential opens these channels, permitting an influx of Ca2+ ions into the cytosol from the extracellular medium. The amount of Ca2+ that enters an axon terminal through voltage-gated Ca2+ channels is sufficient to raise the level of Ca2+ in the region of the cytosol near the synaptic vesicles from <0.1 μM, characteristic of the resting state, to 1 – 100 μM. As we describe below, the Ca2+ ions bind to proteins that connect the synaptic vesicle with the plasma membrane, inducing membrane fusion and thus exocytosis of the neurotransmitter. The extra Ca2+ ions are rapidly pumped out of the cell by Ca2+ ATPases, lowering the cytosolic Ca2+ level and preparing the terminal to respond again to an action potential.

The presence of voltage-gated Ca2+ channels in axon terminals has been demonstrated in neurons treated with drugs that block Na+ channels and thus prevent conduction of action potentials. When the membrane of axon terminals in such treated cells is artificially depolarized, an influx of Ca2+ ions into the neurons occurs and exocytosis is triggered. Patch-clamping experiments show that voltage-gated Ca2+ channels, like voltage-gated Na+ channels, open transiently upon depolarization of the membrane.

Synaptic Vesicles Can Be Filled, Exocytosed, and Recycled within a Minute

Two pools of neurotransmitter-filled synaptic vesicles are present in axon terminals: those “docked” at the plasma membrane, which can be readily exocytosed, and those in reserve in the active zone near the plasma membrane. Each rise in Ca2+ triggers exocytosis of about 10 percent of the docked vesicles. However, this is but one of the series of steps involved in forming synaptic vesicles, filling them with neurotransmitter, moving them to the active zone near the plasma membrane, docking them at the plasma membrane, and then, after vesicle fusion with the plasma membrane, recycling their membrane components by endocytosis (Figure 21-29).

Figure 21-29. Release of neurotransmitters and the recycling of synaptic vesicles.

Figure 21-29

Release of neurotransmitters and the recycling of synaptic vesicles. Vesicles import neurotransmitters (red circles) from the cytosol (step 1) using a H+/neurotransmitter (more...)

Recycling of synaptic-vesicle membrane proteins is rapid, as indicated by the ability of many neurons to fire fifty times a second, and quite specific, in that several membrane proteins unique to the synaptic vesicles are specifically internalized by endocytosis. Endocytosis usually involves clathrin-coated vesicles, though non-clathrin-coated vesicles may also be used. After the endocytic vesicles lose their clathrin coat, however, they usually do not fuse with larger, low pH endosomes, as they do during endocytosis of plasma-membrane proteins in other cells (see Figure 17-46). Rather, the recycled vesicles are immediately refilled with neurotransmitter.

Multiple Proteins Participate in Docking and Fusion of Synaptic Vesicles

Because synaptic vesicles are small and homogeneous in size, they can be readily purified from the brain and their proteins isolated. The synaptic-vesicle membrane contains V-type ATPases, which generate a low intravesicular pH, and a proton-coupled neurotransmitter antiporter, which imports neurotransmitters from the cytosol (see Figure 21-29). Here we focus on synaptic-vesicle and plasma-membrane proteins that function in vesicle docking and fusion. Although the major proteins have been characterized in some detail, the exact functions of many and the order in which they interact still remain unclear.

Synapsin and Other Cytoskeletal Proteins

The axon terminal exhibits a highly organized arrangement of cytoskeletal fibers that is essential for localizing synaptic vesicles to the plasma membrane at the synaptic cleft (Figure 21-30). The vesicles themselves are linked together by synapsin, a fibrous phosphoprotein structurally related to other cytoskeletal proteins that bind the fibrous proteins actin and spectrin (Section 18.1). Synapsin is localized to the cytosolic surface of all synaptic-vesicle membranes and constitutes 6 percent of vesicle proteins. Thicker filaments radiate from the plasma membrane and bind to vesicle-associated synapsin; probably these interactions keep the synaptic vesicles close to the part of the plasma membrane facing the synapse. Indeed, synapsin knockout mice, although viable, are prone to seizures; during repetitive stimulation of many neurons in such mice, the number of synaptic vesicles that fuse with the plasma membrane is greatly reduced. Thus synapsins are thought to recruit synaptic vesicles to the active zone. Because synapsins are substrates of cAMP-dependent and Ca2+-calmodulin – dependent protein kinases, a rise in cytosolic Ca2+ triggers their phosphorylation. This apparently causes the release of synaptic vesicles from the cytoskeleton and increases the number of vesicles available for fusion with the plasma membrane.

Figure 21-30. Micrograph of an axon terminal obtained by the rapid-freezing deep-etch technique.

Figure 21-30

Micrograph of an axon terminal obtained by the rapid-freezing deep-etch technique. Note the fibers, largely composed of synapsin, that interconnect the vesicles and also connect some (more...)

Vesicle Targeting and Fusion Proteins

The same types of proteins discussed in Chapter 17 mediate the targeting and fusion of neurotransmitter-filled vesicles at synapses (Figure 21-31). These include Rab3A, a neuron-specific GTP-binding protein similar in sequence and function to other Rab proteins that control vesicular traffic in the secretory pathway. Rab3A is located in the membrane of synaptic vesicles and appears to be essential for localization of vesicles to the active zone. Rab3A knockout mice, like synapsin knockout mice, are viable, but repetitive stimulation of certain neurons in such mice causes a reduction in the number of synaptic vesicles able to fuse with the plasma membrane.

Figure 21-31. Synaptic-vesicle and plasma-membrane proteins important for vesicle docking and fusion.

Figure 21-31

Synaptic-vesicle and plasma-membrane proteins important for vesicle docking and fusion. Interaction of the T-SNAREs syntaxin and SNAP25 with the V-SNARE VAMP is aided by Rab3A. Neurexin, (more...)

Image med.jpgThe principal V-SNARE in synaptic vesicles isVAMP (vesicle-associated membrane protein), which also is called synaptobrevin. This V-SNARE tightly binds syntaxin and SNAP25, the principal T-SNAREs in the plasma membrane of axon terminals. As in the fusion of other intracellular vesicles with membranes, SNAP proteins and NSF assist in the disassociation of VAMP from T-SNAREs after vesicle fusion (see Figure 17-59). Strong evidence for the role of VAMP is provided by the mechanism of action of botulinum-B toxin, a bacterial protein that can cause the paralysis and death characteristic of botulism,a type of food poisoning. The toxin is composed of two polypeptides: One binds to motor neurons that release acetylcholine at synapses with muscle cells, facilitating entry of the other polypeptide, a protease, into the cytosol. The only protein this protease cleaves is VAMP; destruction of VAMP prevents acetylcholine release at the neuromuscular synapse, causing paralysis.

Ca2+-Sensing Protein

Another protein in the synaptic-vesicle membrane called synaptotagmin contains four Ca2+-binding sites in its cytosolic domain (see Figure 21-31). Several types of evidence support the hypothesis that synaptotagmin is the key Ca2+-sensing protein that triggers vesicle exocytosis. One piece of evidence is that in the presence of phospholipids the affinity of synaptotagmin for Ca2+ is 1 to 100 μM, consistent with concentrations of Ca2+ present in the active zone following opening of voltage-gated Ca2+ channels. Furthermore, injection of protein fragments derived from the cytosolic domain of synaptotagmin into a squid giant axon does not affect vesicle docking but does inhibit Ca2+-stimulated vesicle exocytosis. Presumably these fragments compete with normal synaptotagmin protein for binding to critical target proteins. Additional evidence comes from synaptotagmin mutants of Drosophila and the nematode C. elegans. Embryos that completely lack synaptotagmin fail to hatch and exhibit very reduced, uncoordinated muscle contractions. Larvae with partial loss-of-function mutations of synaptotagmin survive, but their neurons are defective in Ca2+-stimulated vesicle exocytosis.

How synaptotagmin functions is beginning to be understood. At the low cytosolic Ca2+ levels found in resting cells, synaptotagmin apparently binds to a complex of the plasma-membrane proteins neurexin and syntaxin, perhaps facilitating vesicle docking with the membrane. The presence of synaptotagmin, however, blocks binding of other essential fusion proteins to the neurexin-syntaxin complex, thereby preventing vesicle fusion. When synaptotagmin binds Ca2+, it is displaced from the complex, allowing other proteins to bind and thus initiating membrane docking or fusion. Thus synaptotagmin may operate as a “clamp” to prevent fusion from proceeding in the absence of a Ca2+ signal; by binding to proteins and phospholipids in the plasma membrane, it may also facilitate fusion of the two membranes.

Chemical Synapses Can Be Excitatory or Inhibitory

One way of classifying synapses is whether the action of the neurotransmitter tends to promote or inhibit the generation of an action potential in the postsynaptic cell. Binding of a neurotransmitter to an excitatory receptor opens a channel that admits Na+ ions or both Na+ and K+ ions. These non-voltage-gated ion channels can be part of the receptor protein or can be a separate protein that opens in response to a cytosolic signal generated by the activated receptor. Channel opening leads to depolarization of the postsynaptic plasma membrane, promoting generation of an action potential. In contrast, binding of a neurotransmitter to an inhibitory receptor on the postsynaptic cell causes opening of K+ or Cl channels. The resulting membrane hyperpolarization inhibits generation of an action potential in the postsynaptic cell.

As illustrated in Figure 21-32, the same neurotransmitter (e.g., acetylcholine) can produce an excitatory response in some postsynaptic cells and an inhibitory response in others. Many nerve-nerve and most nerve-muscle chemical synapses are excitatory.

Figure 21-32. Excitatory and inhibitory responses in postsynaptic cells stimulated by acetylcholine.

Figure 21-32

Excitatory and inhibitory responses in postsynaptic cells stimulated by acetylcholine. (a) Application of acetylcholine (or nicotine) to frog skeletal muscle produces a rapid postsynaptic (more...)

Two Classes of Neurotransmitter Receptors Operate at Vastly Different Speeds

Neurotransmitter receptors in the plasma membrane of postsynaptic cells fall into two broad classes: ligand-gated ion channels and G protein – coupled receptors. Synapses containing either type can be excitatory or inhibitory, but the two types vary greatly in the speed of their response.

Fast Synapses and Ligand-Gated Ion Channels

The exoplasmic domain of a ligand-gated receptor possesses a neurotransmitter-binding site (see Figure 21-8c). Binding of the neurotransmitter causes an immediate conformational change that opens the channel portion of the protein, allowing ions to cross the membrane and causing the membrane potential to change within 0.1 – 2 milliseconds. Examples of excitatory and inhibitory ligand-gated receptors are listed in Table 21-1. Binding of ligand to excitatory receptors opens cation channels that allow passage of both Na+ and K+ ions, leading to rapid depolarization of the postsynaptic membrane; in contrast, binding of ligand to inhibitory receptors opens Cl channels, leading to hyperpolarization of the postsynaptic plasma membrane (see Figure 21-10).

Table 21-1. Neurotransmitter Receptors That Are Ligand-Gated Ion Channels.

Table 21-1

Neurotransmitter Receptors That Are Ligand-Gated Ion Channels.

Slow Synapses and Receptors Coupled to G Proteins

Many functions of the nervous system operate with time courses of seconds or minutes; regulation of the heart rate, for instance, requires that action of neurotransmitters extend over several beating cycles measured in seconds. In general, the neurotransmitter receptors utilized in slow synap-ses are coupled to G proteins (Table 21-2). The sequence is similar to signaling in non-neuronal cells mediated by G protein – coupled receptors (Chapter 20). In a postsynaptic cell, binding of a neurotransmitter to this type of receptor activates a coupled G protein that, in most cases, directly binds to a separate ion-channel protein, causing an increase or decrease in its ion conductance. In other cases, the receptor-activated G protein activates adenylate cyclase or phospholipase C, triggering a rise in cytosolic cAMP or Ca2+, respectively; these second messengers in turn affect the ion conductance of a linked ion channel. Examples of both types of G protein – coupled receptors are described in later sections. The postsynaptic responses induced by neurotransmitter binding to G protein – coupled receptors are intrinsically slower and longer lasting than those induced by ligand-gated channels. This is illustrated by the differing time scales of the responses to acetylcholine in skeletal muscle and heart muscle (see Figure 21-32).

Table 21-2. Some Neurotransmitter and Neuropeptide Receptors That Are Coupled to G Proteins.

Table 21-2

Some Neurotransmitter and Neuropeptide Receptors That Are Coupled to G Proteins.

As noted earlier, many neurons secrete neuropeptides whose effects tend to extend over a prolonged period. Not surprisingly, the receptors for this class of transmitters are coupled to G proteins (see Table 21-2). As we discuss in a later section, the receptor for light (rhodopsin) and the hundreds of different olfactory receptors that detect odorants also are linked to G proteins.

Acetylcholine and Other Transmitters Can Activate Multiple Receptors

The diversity of receptors for and responses to a single kind of neurotransmitter is illustrated by acetylcholine. Synapses in which acetylcholine is the neurotransmitter are termed cholinergic synapses. Acetylcholine receptors that cause excitatory responses lasting only milliseconds are called nicotinic acetylcholine receptors. They are so named because nicotine, like acetylcholine, causes a rapid depolarization (see Figure 21-32a). As noted already, these receptors are ligand-gated channels for Na+ and K+ ions. Other acetylcholine receptors are called muscarinic acetylcholine receptors because muscarine (a mushroom alkaloid) causes the same response as does acetylcholine. There are several subtypes of muscarinic acetylcholine receptors present in different cell types; all are coupled to G proteins, but they induce different responses. The M2 receptor present in heart muscle activates a Gi protein that causes the opening of a K+ channel and thus a hyperpolarization lasting seconds (see Figure 21-32b). The M1, M3, and M5 subtypes are coupled to other G proteins known as Go or Gq and activate phospholipase C; the M4 subtype activates Gi and inhibits adenylate cyclase. Thus, a single neurotransmitter induces very different responses in different nerve and muscle cells, depending on the type of receptor found in the target cells.

Acetylcholine and the Neuromuscular Junction

Acetylcholine is released by motor neurons at synapses with muscle cells, often called neuromuscular junctions. Like other neurotransmitters, acetylcholine is synthesized in the cytosol of the presynaptic axon terminal and stored in synaptic vesicles. A single axon terminus of a frog motor neuron may contain a million or more synaptic vesicles, each containing 1000 – 10,000 molecules of acetylcholine; these vesicles often accumulate in rows in the active zone (Figure 21-33). Such a neuron can form synapses with a single skeletal muscle cell at several hundred points.

Figure 21-33. Longitudinal section through a frog nerve-muscle synapse (neuromuscular junction).

Figure 21-33

Longitudinal section through a frog nerve-muscle synapse (neuromuscular junction). Synaptic vesicles in the axon terminal are clustered near the region where exocytosis occurs. The (more...)

Acetylcholine is synthesized from acetyl coenzyme A (CoA) and choline in a reaction catalyzed by choline acetyltransferase:

Image ch21e2.jpg

Synaptic vesicles take up and concentrate acetylcholine from the cytosol against a steep concentration gradient, using a H+/acetylcholine antiporter in the vesicle membrane (see Figure 21-29). Curiously, the gene encoding this antiporter is contained entirely within the first intron of the gene encoding choline acetyltransferase, a mechanism conserved throughout evolution for ensuring coordinate expression of these two proteins.

Transmitter-Mediated Signaling Is Terminated by Several Mechanisms

Following release of a neurotransmitter or neuropeptide, it must be removed or destroyed to prevent continued stimulation of the postsynaptic cell. There are three main ways to end the signaling: The transmitter may (1) diffuse away from the synaptic cleft, (2) be taken up by the presynaptic neuron, or (3) be enzymatically degraded. Signaling by acetylcholine and neuropeptides is terminated by enzymatic degradation of the transmitter, but signaling by most of the classic neurotransmitters is terminated by uptake.

Hydrolysis of Acetylcholine

After its release into the synaptic cleft, acetylcholine is hydrolyzed to acetate and choline by the enzyme acetylcholinesterase, which occurs in several forms. The secreted form of this enzyme has a collagen-like subunit that anchors the enzyme to the basal lamina that fills the synaptic cleft between a neuron and muscle cell. The membrane-bound form is inserted into the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor (see Figure 3-36a). Choline produced by hydrolysis of acetylcholine in the synaptic cleft is transported back into the nerve terminal by a Na+/choline symporter, to be used in synthesis of more neurotransmitter. The operation of this transporter is similar to that of the Na+/glucose symporters used to transport glucose into certain cells against a concentration gradient (see Figure 15-19).

Image med.jpgDuring hydrolysis of acetylcholine by acetylcholinesterase, a serine at the active site reacts with the acetyl group forming an enzyme-bound intermediate. A large number of nerve gases and other neurotoxins inhibit the activity of acetylcholinesterase by reacting with the active-site serine. Physiologically, these toxins prolong the action of acetylcholine, thus extending the period of membrane depolarization. Such inhibitors can be lethal if they prevent relaxation of the muscles necessary for breathing.

Uptake of Neurotransmitters

With the exception of acetylcholine, all the neurotransmitters shown in Figure 21-28 are removed from the synaptic cleft by transport into the axon terminals that released them. Thus these transmitters are recycled intact. Transporters for GABA, norepinephrine, dopamine, and serotonin were the first to be cloned and studied. These four are encoded by a gene family, and are 60 – 70 percent identical in their amino acid sequences. Each transporter is thought to have 12 membrane-spanning α helices. All are Na+/neurotransmitter symporters, and frequently Cl is transported along with the neurotransmitter. As with other Na+ symporters, the movement of Na+ into the cell down its electrochemical gradient provides the energy for uptake of the neurotransmitter (see Figure 15-9). Study and cloning of these transporters was facilitated by the observation that, following microinjection of mRNA from regions of the brain into frog oocytes, functional transporters for these neurotransmitters were expressed on the oocyte plasma membrane.

Image med.jpgThe norepinephrine, serotonin, and dopamine transporters are all inhibited by cocaine. Binding of cocaine to the dopamine transporter inhibits dopamine uptake, thus prolonging signaling at key brain synapses; indeed, the dopamine transporter is the principal brain “cocaine receptor.” Therapeutic agents such as the antidepressant drugs fluoxetine (Prozac) and imipramine block serotonin uptake, and the tricyclic antidepressant desipramine blocks norepinephrine uptake. However, the precise role of transporters in the antidepressant action of these drugs is not yet clear.

Impulses Transmitted across Chemical Synapses Can be Amplified and Computed

Chemical synapses have two important advantages over electric ones in the transmission of impulses from a presynaptic cell. The first is signal amplification, which is common at nerve- muscle synapses. An action potential in a single presynaptic motor neuron can cause contraction of multiple muscle cells because release of relatively few signaling molecules at a synapse is all that is required to stimulate contraction.

The second advantage is signal computation, which is common at synapses involving interneurons, especially in the central nervous system. A single neuron can be affected simultaneously by signals received at multiple excitatory and inhibitory synapses (see Figure 21-3). The neuron continuously averages these signals and determines whether or not to generate an action potential. In this process, the various depolarizations and hyperpolarizations generated at synapses move by passive spread along the plasma membrane from the dendrites to the cell body and then to the axon hillock, where they are summed together. An action potential is generated whenever the membrane at the axon hillock becomes depolarized to a certain voltage called the threshold potential (Figure 21-34). Thus an action potential is generated in an all-or-nothing fashion: Depolarization to the threshold always leads to an action potential, whereas any depolarization that does not reach the threshold potential never induces it.

Figure 21-34. The threshold potential for generation of an action potential in a postsynaptic cell.

Figure 21-34

The threshold potential for generation of an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. (more...)

Whether a neuron generates an action potential in the axon hillock depends on the balance of the timing, amplitude, and localization of all the various inputs it receives; this signal computation differs for each type of interneuron. In a sense, each neuron is a tiny computer that averages all the receptor activations and electric disturbances on its membrane and makes a decision whether to trigger an action potential and conduct it down the axon. An action potential will always have the same magnitude in any particular neuron. The frequency with which action potentials are generated in a particular neuron is the important parameter in its ability to signal other cells.

Impulse Transmission across Electric Synapses Is Nearly Instantaneous

In an electric synapse, ions move directly from one neuron to another via gap junctions (Figure 21-35). The membrane depolarization associated with an action potential in the presynaptic cell passes through the gap junctions, leading to a depolarization, and thus an action potential, in the postsynaptic cell. Such cells are said to be electrically coupled. In the heart, for example, electric synapses allow groups of muscle cells to contract in synchrony. Gap junctions also connect nonexcitable cells, enabling small molecules such as cAMP and amino acids to pass from one cell to another (see Figure 22-8).

Figure 21-35. An electric synapse.

Figure 21-35

An electric synapse. (a) The plasma membranes of the presynaptic and postsynaptic cells are linked by gap junctions. Flow of ions through these channels allows electric impulses to be transmitted (more...)

Electric synapses also have the advantage of speed and certainty; the direct transmission of impulses avoids the delay of about 0.5 ms that is characteristic of chemical synapses (Figure 21-36). In certain circumstances, this fraction of a millisecond advantage can mean the difference between life and death. Electric synapses in the goldfish brain, for example, mediate a reflex action that flaps the tail, which permits a fish to escape from predators. Examples also exist of electric coupling between groups of cell bodies and dendrites, ensuring simultaneous depolarization of an entire group of coupled cells. The large number of electric synapses in many cold-blooded fishes suggests that they may be an adaptation to low temperatures, as the lowered rate of cellular metabolism in the cold reduces the rate of impulse transmission across chemical synapses.

Figure 21-36. Transmission of action potentials across electric and chemical synapses.

Figure 21-36

Transmission of action potentials across electric and chemical synapses. In both cases, the presynaptic neuron was stimulated and the membrane potential was measured in both the presynaptic (more...)

SUMMARY

  •  At chemical synapses, impulses are transmitted by the release of neurotransmitters from the axon terminal of the presynaptic cell into the synaptic cleft. Their subsequent binding to specific receptors on the postsynaptic cell causes a change in the ion permeability and thus the potential of the postsynaptic plasma membrane.
  •  Classic low-molecular-weight neurotransmitters are imported from the cytosol into synaptic vesicles by a proton-coupled antiporter. V-type ATPases maintain the low intravesicular pH that powers neurotransmitter import.
  •  Arrival of an action potential at a presynaptic axon terminal opens voltage-gated Ca2+ channels, inducing a localized rise in the cytosolic Ca2+ level that triggers exocytosis of synaptic vesicles. Following neurotransmitter release, vesicles are endocytosed and recycled (see Figure 21-29).
  •  Multiple cytosolic proteins including synapsin recruit synaptic vesicles to the active zone of the plasma membrane adjacent to the synaptic cleft.
  •  The principal V-SNARE in synaptic vesicles is VAMP (synaptobrevin), which tightly binds the principal plasma-membrane T-SNAREs — syntaxin and SNAP25 — with the assistance of Rab3A and other docking and fusion proteins (see Figure 21-31). Synaptotagmin in the synaptic-vesicle membrane is thought to be the key Ca2+-sensing protein that triggers exocytosis.
  •  Stimulation of excitatory receptors by neurotransmitter binding causes depolarization of the postsynaptic plasma membrane, promoting generation of an action potential. Conversely, stimulation of inhibitory receptors causes hyperpolarization of the postsynaptic membrane, repressing generation of an action potential.
  •  Neurotransmitter receptors that are ligand-gated channels induce rapid (millisecond) responses, whereas those that are coupled to G proteins induce responses that last seconds or more. Depending on the specific receptor, the same neurotransmitter can induce either an excitatory or inhibitory response.
  •  Removal of neurotransmitters from the synaptic cleft occurs by enzymatic degradation, re-uptake into the presynaptic cell, or diffusion.
  •  Chemical synapses allow a single postsynaptic cell to amplify, modify, and compute excitatory and inhibitory signals received from multiple presynaptic neurons. Such integration is common in the central nervous system.
  •  Postsynaptic cells generate action potentials in an all-or-nothing fashion when the plasma membrane at the axon hillock is depolarized to the threshold potential by the summation of small depolarizations and hyperpolarizations caused by activation of multiple neuronal receptors (see Figure 21-34).
  •  At electric synapses, ions pass directly from the presynaptic cell to the postsynaptic cell through gap junctions. These synapses are much less common than chemical synapses.
  •  Impulse transmission at chemical synapses occurs with a small time delay but is nearly instantaneous at electric synapses.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, W. H. Freeman and Company.
Bookshelf ID: NBK21521