CHEMICAL SYNAPTIC TRANSMISSION
Chemical synaptic transmission proceeds in three steps: (1) The release of the transmitter substance from the bouton in response to the arrival of an action potential, (2) The change in the ionic permeabilities of the post-synaptic membrane caused by the transmitter, and (3) the removal of the transmitter from the synaptic cleft. Depending on the type of permeability changes produced in the second step, synaptic activation may have either an excitatory or an inhibitory effect on the post-synaptic cell.
Synaptic transmitter substances are
concentrated in synaptic vesicles within the bouton. Although the exact
mechanism of its release is unknown, it appears that the transmitter substance
is released in packets, or quanta, of 1,000 to 10,000 molecules at a time, and
that the probability of release of these quanta increases with the degree of
depolarization of the terminal membrane. Thus the intense depolarization caused
by an action potential actuates the nearly simultaneous release of a large
number of quanta. A reasonable hypothesis to account for the quantal nature of
transmitter release is that the contents of an entire vesicle are discharged at
once into the synaptic cleft, perhaps by the process of exocytosis.
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| Plate 2-15 |
After their release, transmitter
molecules diffuse across the synaptic cleft and combine with specific receptor
molecules in the postsynaptic membrane. This combination gives rise to a change
in the ionic permeability of the postsynaptic membrane and results in a flow of
ions down their electrochemical potential gradients. This ionic flow is not
synchronous with the arrival of the action potential in the terminal but begins
after a synaptic delay of 0.3 to 0.5 msec, which is the time required
for transmitter release and diffusion and for the completion of reactions
within the postsynaptic membrane, which alter membrane permeability.
The direction of current flow
produced by transmitter action depends upon which ionic permeabilities are
altered. In an excitatory synapse, the transmitter causes an increase in
the permeability of the postsynaptic membrane to sodium ions (Na+)
and potassium ions (K+). Because of their respective concentration
gradients across the neuronal membrane (see Plate 2-15), Na+ tends to move into the postsynaptic cell, and K+,
out of it. The negative potential of the neuronal cytoplasm, however, assists
the inward flow of positive ions and retards their outward flow so that the
combined electrochemical force for Na+ influx greatly exceeds that
for K+ efflux. Thus the predominant ionic movement across the
postsynaptic membrane is an inward flow of Na+. As shown, the resulting
current flow causes a shift of the postsynaptic cell membrane potential in the
depolarizing direction. This depolarizing potential change, which is called an excitatory
postsynaptic potential (EPSP), brings the postsynaptic cell closer to its
threshold for action potential initiation.
In an inhibitory synapse,
transmitter action causes an increase of
the postsynaptic membrane’s permeability to K+ and chloride ions (Cl−)
but not to Na+. Because Cl− is approximately at
electrochemical equilibrium across the neuronal membrane, the major ionic
movement is an outward flow of K+. The resulting current flow
is in the opposite direction to that of the current flow in an excitatory
synapse, and gives rise to a shift of the postsynaptic cell membrane potential
in the hyperpolarizing direction. This hyperpolarizing potential change, which
is called an inhibitory postsynaptic potential
(IPSP), moves the membrane
potential away from the threshold for action potential initiation. The
increased ionic permeability of the postsynaptic membrane also contributes to
the inhibitory effect by tending to “short out” any membrane depolarization
occurring simultaneously.
The ionic current and the resulting
membrane potential change have different time courses because the synaptic current charges the membrane
capacitance, which then discharges passively over a period of 10 to 15 msec.
The short duration of the synaptic current is the consequence of the removal of
transmitter from the synaptic cleft. This removal is accomplished in part by
passive diffusion and in part by specific mechanisms that lead to transmitter
uptake by surrounding cells or transmitter breakdown by enzymatic degradation.
