The calcium hypothesis and modulation of transmitter release by hyperpolarizing pulses.

Small presynaptic conditioning hyperpolarizing pulses reduce transmitter release to a depolarizing stimulus by a substantial amount, with little effect on release by a subsequent depolarization. This result, obtained at neuromuscular junctions and the squid giant synapse, has been offered as a disproof of the calcium hypothesis of transmitter release or the residual calcium hypothesis of synaptic facilitation. However, calculations based on several formulations of these hypotheses are shown to be consistent with the experimental results, and no fundamental modification of the hypotheses is necessary.