Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

channels and the electrical PROPERTIES of membranes
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chemical synapses. The channels are concentrated in a specialized region of the
postsynaptic plasma membrane at the synapse and open transiently in response
to the binding of neurotransmitter molecules, thereby producing a brief permeability
change in the membrane (see Figure 11–36A). Unlike the voltage-gated
channels responsible for action potentials, transmitter-gated channels are relatively
insensitive to the membrane potential and therefore cannot by themselves
produce a self-amplifying excitation. Instead, they produce local permeability
increases, and hence changes of membrane potential, that are graded according
to the amount of neurotransmitter released at the synapse and how long it persists
there. Only if the summation of small depolarizations at this site opens sufficient
numbers of nearby voltage-gated cation channels can an action potential be triggered.
This may require the opening of transmitter-gated ion channels at numerous
synapses in close proximity on the target nerve cell.
Chemical Synapses Can Be Excitatory or Inhibitory
Transmitter-gated ion channels differ from one another in several important ways.
First, as receptors, they have highly selective binding sites for the neurotransmitter
that is released from the presynaptic nerve terminal. Second, as channels, they
are selective in the type of ions that they let pass across the plasma membrane;
this determines the nature of the postsynaptic response. Excitatory neurotransmitters
open cation channels, causing an influx of Na + , and in many cases Ca 2+ ,
that depolarizes the postsynaptic membrane toward the threshold potential for
firing an action potential. Inhibitory neurotransmitters, by contrast, open either
Cl – channels or K + channels, and this suppresses firing by making it harder for
excitatory neurotransmitters to depolarize the postsynaptic membrane. Many
transmitters can be either excitatory or inhibitory, depending on where they are
released, what receptors they bind to, and the ionic conditions that they encounter.
Acetylcholine, for example, can either excite or inhibit, depending on the type
of acetylcholine receptors it binds to. Usually, however, acetylcholine, glutamate,
and serotonin are used as excitatory transmitters, and γ-aminobutyric acid (GABA)
and glycine are used as inhibitory transmitters. Glutamate, for instance, mediates
most of the excitatory signaling in the vertebrate brain.
We have already discussed how the opening of Na + or Ca 2+ channels depolarizes
a membrane. The opening of K + channels has the opposite effect because
the K + concentration gradient is in the opposite direction—high concentration
inside the cell, low outside. Opening K + channels tends to keep the cell close to
the equilibrium potential for K + , which, as we discussed earlier, is normally close
to the resting membrane potential because at rest K + channels are the main type
of channel that is open. When additional K + channels open, it becomes harder to
drive the cell away from the resting state. We can understand the effect of opening
Cl – channels similarly. The concentration of Cl – is much higher outside the
cell than inside (see Table 11–1, p. 598), but the membrane potential opposes its
influx. In fact, for many neurons, the equilibrium potential for Cl – is close to the
resting potential—or even more negative. For this reason, opening Cl – channels
tends to buffer the membrane potential; as the membrane starts to depolarize,
more negatively charged Cl – ions enter the cell and counteract the depolarization.
Thus, the opening of Cl – channels makes it more difficult to depolarize the
membrane and hence to excite the cell. Some powerful toxins act by blocking the
action of inhibitory neurotransmitters: strychnine, for example, binds to glycine
receptors and prevents their inhibitory action, causing muscle spasms, convulsions,
and death.
However, not all chemical signaling in the nervous system operates through
these ionotropic ligand-gated ion channels. In fact, most neurotransmitter molecules
that are secreted by nerve terminals, including a large variety of neuropeptides,
bind to metabotropic receptors, which regulate ion channels only
indirectly through the action of small intracellular signal molecules (discussed
in Chapter 15). All neurotransmitter receptors fall into one or other of these two