THE SYNAPSE & SYNAPTIC POTENTIALS
The communication between neurons in the CNS occurs through chemical synapses in the majority of cases. (A few instances of electrical coupling between neurons have been documented, and such coupling may play a role in synchronizing neuronal dis-charge. However, it is unlikely that these electrical synapses are an important site of drug action.) The events involved in synaptic transmission can be summarized as follows.
An action potential in the presynaptic fiber propagates into the synaptic terminal and activates voltage-sensitive calcium channels in the membrane of the terminal (see Figure 6–3). The calcium chan-nels responsible for the release of transmitter are generally resistant to the calcium channel-blocking agents discussed earily (verapamil, etc) but are sensitive to blockade by certain marine toxins and metal ions (see Tables 21–1 and 12–4). Calcium flows into the terminal, and the increase in intraterminal calcium concentration promotes the fusion of synaptic vesicles with the presynaptic mem-brane. The transmitter contained in the vesicles is released into the synaptic cleft and diffuses to the receptors on the postsynaptic mem-brane. Binding of the transmitter to its receptor causes a brief change in membrane conductance (permeability to ions) of the postsynaptic cell. The time delay from the arrival of the presynaptic action poten-tial to the onset of the postsynaptic response is approximately 0.5 ms. Most of this delay is consumed by the release process, par-ticularly the time required for calcium channels to open.
The first systematic analysis of synaptic potentials in the CNS was in the early 1950s by Eccles and associates, who recorded intra-cellularly from spinal motor neurons. When a microelectrode enters a cell, there is a sudden change in the potential recorded by the electrode, which is typically about –70 mV (Figure 21–3). This is the resting membrane potential of the neuron. Two types of pathways— excitatory and inhibitory—impinge on the motor neuron.
When an excitatory pathway is stimulated, a small depolariza-tion or excitatory postsynaptic potential (EPSP) is recorded. This potential is due to the excitatory transmitter acting on an ionotropic receptor, causing an increase in cation permeability. Changing the stimulus intensity to the pathway, and therefore the number of presynaptic fibers activated, results in a graded change in the size of the depolarization. When a sufficient number of excitatory fibers are activated, the excitatory postsynaptic potential depolarizes the postsynaptic cell to threshold, and an all-or-none action potential is generated.
When an inhibitory pathway is stimulated, the postsynaptic membrane is hyperpolarized owing to the selective opening of chloride channels, producing an inhibitory postsynaptic poten-tial (IPSP) (Figure 21–4). However, because the equilibriumpotential for chloride is only slightly more negative than the rest-ing potential (∼ –65 mV), the hyperpolarization is small and contributes only modestly to the inhibitory action. The opening of the chloride channel during the inhibitory postsynaptic poten-tial makes the neuron “leaky” so that changes in membrane poten-tial are more difficult to achieve. This shunting effect decreases the change in membrane potential during the excitatory postsynaptic potential. As a result, an excitatory postsynaptic potential that evoked an action potential under resting conditions fails to evoke an action potential during the inhibitory postsynaptic potential (Figure 21–4). A second type of inhibition is presynaptic inhibi-tion. It was first described for sensory fibers entering the spinalcord, where excitatory synaptic terminals receive synapses called axoaxonic synapses (described later). When activated, axoaxonic synapses reduce the amount of transmitter released from the ter-minals of sensory fibers. It is interesting that presynaptic inhibi-tory receptors are present on almost all presynaptic terminals in the brain even though axoaxonic synapses appear to be restricted to the spinal cord. In the brain, transmitter spills over to neighbor-ing synapses to activate the presynaptic receptors.