Some Consequences of Intracellular Calcium Binding on Phasic Synaptic Transmitter Release

Until recently, no mechanism has been offered to account simultaneously for phasic release of transmitter and its facilitation at the frog neuromuscular junction. Katz & Miledi (1) showed that external calcium was necessary at the time of the first nerve impulse and suggested that calcium entered the terminal and, by binding to some receptor site at the presynaptic terminal, released transmitter. The “residual calcium” hypothesis for facilitation evolved from their suggestion (2) that a residuum of “active calcium” remains within the terminal following an action potential for several milliseconds and is able to enhance the amount of transmitter released by succeeding stimuli.