Release kinetics as a tool to describe drug effects on neurotransmitter release

A procedure is developed wherein the time course of neurotransmitter release is used to discern the mechanism of effects of drugs on the release process. It is shown, in agreement with experiments, that the time course of release is insensitive to the temporal distribution of intracellular Ca²⁺ concentration. The time course is also invariant to the steps in the release process that are Ca²⁺ dependent. The most influential events in determining the time course of release are shown to be the steps associated with the slowest forward rate constant and all the backward steps. The procedure was examined for its ability to explain the effects on release of the poison curare and those of temperature. It appears that curare probably blocks release by lowering the rate constant associated with the rate limiting step in release. Increasing temperature is predicted to increase both the forward and the backward rate constants, but not to the same extent.