Feasibility of a Sustained Steep Ca2+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 Ca2+release from intracellular stores, followed by Ca2+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 Ca2+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 Ca2+gradient in the cytosol with high values of Ca2+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.