Feasibility of a sustained steep Ca(2+)Gradient in the cytosol of electrically non-excitable cells.

In electrically non-excitable cells the predominant mode of calcium signaling is a biphasic rise in cytosolic calcium concentration. It results from Ca(2+)release from intracellular stores, followed by Ca(2+)influx across the plasma membrane. It has been hypothesized that prolonged calcium influx may result in a sustained local elevation of the cytosolic calcium concentration near the plasma membrane. The mathematical model presented here evaluates the cytosolic concentration of Ca(2+)as a function of time and distance from the plasma membrane. It consists of cytoplasmic calcium stores and a plasma membrane, both equipped with calcium channels and pumps, and an immobile cytoplasmic calcium buffer. The model has verified quantitatively the feasibility of a stable Ca(2+)gradient in the cytosol with high values of Ca(2+)concentration near the plasma membrane and evaluated its properties as a function of different cellular parameters. The formation of the gradient does not require special distribution of the intracellular contents, channels and pumps. However, it requires buffering of the cytosolic calcium by the intracellular stores and that the rate of calcium release from the stores near the plasma membrane be higher than in other parts of the cell. We suggest that this model can provide an adequate description of the elevated calcium plateau generally observed in electrically non-excitable cells.

A realistic model of biphasic calcium transients in electrically nonexcitable cells.

In many electrically nonexcitable cells, the release of calcium from internal stores is followed by a much slower phase in which the intracellular calcium concentration decreases gradually to a sustained value higher than the concentration before stimulation. This elevated calcium 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 by a membrane receptor; a fast cytoplasmic calcium buffer; and calcium pumps in both the calcium store and cellular membranes. Inherent difficulties in the numerical evaluation of the model, caused by very large calcium fluxes across the store membrane, were overcome by analytically separating the fast processes of calcium release from the slower processes of calcium cycling across the plasma membrane. This enabled the 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 level of cell excitation of the maximum rise in cytoplasmic calcium concentration, the level of the elevated calcium plateau, and the rate of calcium decay. Using the model, we simulated the washout of agonist from the bathing solution and the depletion of the calcium store by a pharmacological agent (such as thapsigargin) under several experimental conditions.