The Synapse & Synaptic Potentials

The communication between neurons in the CNS occurs through chemical synapses in the majority of cases. 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. The calcium channels responsible for the release of transmitter are generally resistant to the calcium channel-blocking agents (verapamil, etc) but are sensitive to blockade by certain marine toxins and metal ions. Calcium flows into the terminal, and the increase in intraterminal calcium concentration promotes the fusion of synaptic vesicles with the presynaptic membrane. The transmitter contained in the vesicles is released into the synaptic cleft and diffuses to the receptors on the postsynaptic membrane. 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 potential to the onset of the postsynaptic response is approximately 0.5 ms. Most of this delay is consumed by the release process, particularly the time required for calcium channels to open.

When an excitatory pathway is stimulated, a small depolarization 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 cause the opening of Cl^– channels, producing an inhibitory postsynaptic potential (IPSP). However, because the equilibrium potential for Cl^– is only slightly more negative than the resting potential (~ –65 mV), the hyperpolarization is small and contributes only modestly to the inhibitory action. The opening of the Cl^– channel during the inhibitory postsynaptic potential makes the neuron "leaky" so that changes in membrane potential 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. 

A second type of inhibition is presynaptic inhibition. It was first described for sensory fibers entering the spinal cord, where excitatory synaptic terminals receive synapses called axoaxonic synapses. When activated, axoaxonic synapses reduce the amount of transmitter released from the terminals of sensory fibers. It is interesting that presynaptic inhibitory 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 neighboring synapses to activate the presynaptic receptors.

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