Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse.

1. The roles of presynaptic calcium influx and calcium accumulation in synaptic facilitation and depression were explored at the giant synapse in the stellate ganglion of the squid. 2. Calcium currents were recorded in the presynaptic terminal, using a three-electrode voltage clamp and blocking sodium and potassium currents pharmacologically. The calcium influx was constant during pairs or trains of brief depolarizing pulses that elicited facilitating or depressing excitatory post-synaptic potentials (e.p.s.p.s). 3. The relationship between calcium influx and transmitter release during brief depolarizing pulses of varying amplitude resembled a power function with exponent of about 2. 4. Presynaptic calcium concentration transients were measured by injecting the dye arsenazo III and detecting absorbance changes microspectrophotometrically. Increments in intracellular free calcium accompanying single action potentials appeared constant for repeated action potentials that elicited facilitating e.p.s.p.s. 5. The presynaptic calcium concentration remains elevated for several seconds following action potentials. 6. Presynaptic injection of calcium ions by interbarrel ionophoresis evokes a postsynaptic depolarization, apparently reflecting a large increase in miniature e.p.s.p. frequency. Presynaptic action potentials remain unaffected by this treatment, but e.p.s.p.s triggered by them are facilitated for several seconds, and then depressed. 7. The results are consistent with the hypothesis that synaptic facilitation is due to the action of residual calcium or a calcium complex remaining in the presynaptic terminal after electrical activity. The late depression of release during calcium injection may be a result of the continual release of transmitter and consequent depletion of a presynaptic store.