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Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
Correspondence: Address reprint requests to Dr. Gary J. Kargacin, Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1 Canada. Tel.: 403-220-3873; Fax: 403-270-2211; E-mail: kargacin{at}ucalgary.ca.
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.
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