Theory of fast neurotransmitter release control based on voltage-dependent interaction between autoreceptors and proteins of the exocytotic machinery.

A molecular-level theory is constructed for the control of fast neurotransmitter release, based on recent experimental findings that depolarization shifts presynaptic autoreceptors to a low affinity state and that an autoreceptor must be bound to a transmitter before it can become associated with the exocytotic apparatus. It is assumed that such an association blocks release; experimental support for this assumption is cited. The theory provides mechanisms for key experimental results concerning the essence of the matter, what controls the time course of evoked release? The same general model can account for both evoked and spontaneous release. The new theory can be regarded as a molecular implementation of the (phenomenological) calcium-voltage hypothesis that was suggested earlier.