Spatial distribution of calcium entry evoked by single action potentials within the presynaptic active zone

The nature of presynaptic calcium (Ca2+) signals that initiate neurotransmitter release makes these signals difficult to study, in part because of the small size of specialized active zones within most nerve terminals. Using the frog motor nerve terminal, which contains especially large active zones, we show that increases in intracellular Ca2+ concentration within 1 msec of action potential invasion are attributable to Ca2+ entry through N-type Ca2+ channels and are not uniformly distributed throughout active zone regions. Furthermore, changes in the location and magnitude of Ca2+ signals recorded before and after experimental manipulations (omega-conotoxin GVIA, diaminopyridine, and lowered extracellular Ca2+) support the hypothesis that there is a remarkably low probability of a single Ca2+ channel opening within an active zone after an action potential. The trial-to-trial variability observed in the spatial distribution of presynaptic Ca2+ entry also supports this conclusion, which differs from the conclusions of previous work in other synapses.