Ca2+ Regulation in the Near-Membrane Microenvironment in Smooth Muscle Cells

Abstract

The microenvironment between the plasma membrane and the near-membrane sarcoplasmic reticulum (SR) may play an important role in Ca2+ regulation in smooth muscle cells. We used a three-dimensional mathematical model of Ca2+ diffusion and regulation and experimental measurements of SR Ca2+ uptake and the distribution of the SR in isolated smooth muscle cells to predict the extent that the near-membrane SR could load Ca2+ after the opening of single plasma membrane Ca2+ channels. We also modeled the effect of SR uptake on 1), single-channel Ca2+ transients in the near-membrane space; 2), the association of Ca2+ with Ca2+ buffers in this space; and 3), the amount of Ca2+ reaching the central cytoplasm of the cell. Our results indicate that, although single-channel Ca2+ transients could increase SR Ca2+ to a certain extent, SR Ca2+ uptake is not rapid enough to greatly affect the magnitude of these transients or their spread to the central cytoplasm unless the Ca2+ uptake rate of the peripheral SR is an order-of-magnitude higher than the mean rate derived from our experiments. Immunofluorescence imaging, however, did not reveal obvious differences in the density of SR Ca2+ pumps or phospholamban between the peripheral and central SR in smooth muscle cells.