Dynamics of intracellular calcium and its possible relationship to phasic transmitter release and facilitation at the frog neuromuscular junction.

We have developed a mechanistic model for intracellular influx, diffusion, and efflux of calcium, and we compare its predictions to the dynamics of transmitter release at the frog's motor nerve terminal. The model includes a square wave influx of calcium, a linear or saturable pump for the efflux of calcium, and slow diffusion of calcium within the terminal due to rapid equilibrium binding of the major portion of the influx to fixed, nonsaturable sites in the cytoplasm. Transmitter release is taken as proportional to the fourth power of the calcium concentration in a region within 100 A of the surface membrane. The model predicts phasic release of transmitter with a time course similar to that of the endplate current--it turns on with a lag, rises rapidly to a peak, and then declines more slowly. It also predicts facilitation, the increased transmitter release in response to a second stimulus for many milliseconds after the initial transmitter release has ceased. This facilitation is similar to that reported at the frog neuromuscular junction in its initial amplitude and time course.