A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement.

Augmentation and posttetanic potentiation--two forms of short-term synaptic enhancement produced by repetitive presynaptic action potentials--are dependent on the buildup and decay of nerve terminal residual calcium that occurs on the seconds to minutes time scale. With the goal of providing a quantitative understanding of these kinetics, we measured the buildup and decay of calcium ions in nerve terminals at the crayfish neuromuscular junction under a variety of intracellular buffer conditions and stimulation paradigms. The calcium extrusion process in the terminals was characterized by analysis of calcium levels reached during long stimulus trains as a function of action potential frequency. The extrusion was linearly dependent on the free calcium ion concentration. Using this result, we developed a mathematical model and computer simulation of the residual calcium kinetics. The model demonstrates the experimentally observed dependence of decay rate on exogenous calcium buffer concentration, and can be explicitly solved to provide an expression for the limiting exponential time course of calcium decay following trains in terms of calcium buffer and extrusion characteristics. Methods to determine the calcium influx per action potential, characteristics of endogenous buffer, and the rate of calcium extrusion are suggested by our analysis and demonstrated experimentally.