A REALISTIC MODEL OF BIPHASIC CALCIUM TRANSIENTS IN ELECTRICALLY NONEXCITABLE CELLS

In many electrically nonexcitable cells, the release of calcium from i nternal stores is followed by a much slower phase in which the intrace llular calcium concentration decreases gradually to a sustained value higher than the concentration before stimulation. This elevated calciu m plateau has been shown to be the result of calcium influx. The model presented in this work describes a system consisting of a cytoplasmic calcium store and a plasma membrane calcium channel, both excitable b y a membrane receptor; a fast cytoplasmic calcium buffer; and calcium pumps in both the calcium store and cellular membranes. Inherent diffi culties in the numerical evaluation of the model, caused by very large calcium fluxes across the store membrane, were overcome by analytical ly separating the fast processes of calcium release from the slower pr ocesses of calcium cycling across the plasma membrane. This enabled th e simulation of realistic biphasic calcium transients similar to those observed experimentally. The model predicted 1) a strong correlation between the rate of calcium cycling across the plasma membrane and the rate of calcium decay; and 2) a dependence on the revel of cell excit ation of the maximum rise in cytoplasmic calcium concentration, the le vel of the elevated calcium plateau, and the rate of calcium decay. Us ing the model, we simulated the washout of agonist from the bathing so lution and the depletion of the calcium store by a pharmacological age nt (such as thapsigargin) under several experimental conditions.