Some Properties of Calcium Current in Mouse Motor Endings

Abstract

It is now well established that the chain of events leading to phasic transmitter release by nerve endings is triggered by Ca²⁺ influx through channels activated by depolarization of the presynaptic membrane. Direct evidence for this has been obtained by Llinas et al (1), in the giant synapse of the squid. Little is known, however, about the relationship between membrane currents and transmitter release in vertebrate endings whose small size prevents a direct approach to presynaptic events. For this reason, many of the basic concepts used to describe excitation-secretion coupling in vertebrate synapses come from the study of postsynaptlc responses in neuromuscular junctions. Here, acetylcholine (Ach) release is a brief event that occurs 0.5 – 1 ms (at room temperature) after arrival of nerve impulses to motor endings (2,3). Since both Ach diffusion in the cleft and interaction with postsynaptic receptors are very fast processes, most of the synaptic delay would appear to be caused by Ca channel opening and by the release mechanism itself. Little is known about the kinetics of opening and closing of Ca channels in vertebrate synapses, although an extrapolation from the data obtained by Llinas et al (4) in the giant synapse of the squid suggests that Ca channels start conducting a little before the peak of the action potential and begin closing down near the halfway point of its repolarizing phase. Indeed, experiments reported by Katz & Miledi (2) showed that a hyperpolarizing pulse delivered by a focal electrode to frog nerve terminals during the decay of a nerve-evoked action potential suppresses transmitter release, presumably by Ca channel closure upon membrane repolarization. If the hyperpolarizing pulse was delivered a little later, no effect on transmitter release was observed. Thus, it is likely that Ca²⁺ enters presynaptic membrane for a very short period of time. Unfortunately, because of the small size of vertebrate endings, direct evidence for the relationship between Ca²⁺ influx and transmitter release has been missing until now.