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At the squid giant synapse, a presynaptic action potential is accompanied by an influx of calcium ions that continue to be detectable with arsenazo III microspectrophotometry for several seconds. Nevertheless, transmitter release occurs phasically, lasting only about 2 msec. If a second action potential follows within about 100 msec after the first, it releases more transmitter. In this paper, we present a mathematical model of intracellular calcium diffusion with binding to fixed cytoplasmic sites, active extrusion at the surface, and influx during an action potential, to predict the distribution of intracellular calcium following an action potential. With a square law relation between submembrane calcium and transmitter release, the model predicts the phasic release of transmitter and the magnitude and time course of synaptic facilitation following an action potential, as well as the relatively long persistence of free intracellular calcium.

Presynaptic calcium diffusion and the time courses of transmitter release and synaptic facilitation at the squid giant synapse