Voltage Dependent Release of Neurotransmitter

One of the most interesting aspects of synaptic transmission is the mechanism by which an action potential in the presynaptic terminal triggers the release of the chemical transmitter substance. One possibility is that transmitter release is due to some aspect of the sequence of permeability changes underlying the action potential in the presynaptic terminal. The action potential is associated with a slight influx of Na+ and a slight efflux of K+. Perhaps in some way either the small influx of Na+ or efflux of K+ disturbs the intracellular environment and causes the release of transmitter.

Figure 13 illustrates an experiment to examine this hypothesis. Rather than using the neuromuscular junction, a more advantageous experimental preparation, the squid giant synapse, is used. The squid giant synapse is so large that the presynaptic terminal can be impaled with two electrodes: one to record the presynaptic potential and the other to depolarize the terminal artificially (Fig. 14) (this is not possible at the skeletal neuromuscular junction). A third electrode is used to record the potential changes in the postsynaptic cell. To examine the possible roles of Na+ influx and K+ efflux in triggering release, the preparation is exposed to TTX (to block Na+ influx) and tetraethylammonium (TEA) (to block K+ efflux). By passing brief current pulses of various amplitudes into the stimulating electrode, the membrane potential of the presynaptic terminal can be depolarized to a variety of different membrane potentials without initiating action potentials (Fig. 13). When the presynaptic cell is depolarized by a small amount, there is no postsynaptic potential. A striking observation is made, however, when greater levels of depolarization are applied. In this case, postsynaptic potentials are produced, and their amplitudes depend on the level of depolarization. Thus, this experiment indicates that transmitter release is voltage dependent and that artificial depolarization of the presynaptic terminal is able to produce a postsynaptic potential. Because the preparation has been treated with TTX and TEA, this experiment clearly demonstrates that the voltage-dependent changes in Na+ and K+ permeability that

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