Bazzazi Hojjat, Kargacin Margaret E, Kargacin Gary J
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
Biophys J. 2003 Sep;85(3):1754-65. doi: 10.1016/S0006-3495(03)74605-0.
The microenvironment between the plasma membrane and the near-membrane sarcoplasmic reticulum (SR) may play an important role in Ca(2+) regulation in smooth muscle cells. We used a three-dimensional mathematical model of Ca(2+) diffusion and regulation and experimental measurements of SR Ca(2+) uptake and the distribution of the SR in isolated smooth muscle cells to predict the extent that the near-membrane SR could load Ca(2+) after the opening of single plasma membrane Ca(2+) channels. We also modeled the effect of SR uptake on 1), single-channel Ca(2+) transients in the near-membrane space; 2), the association of Ca(2+) with Ca(2+) buffers in this space; and 3), the amount of Ca(2+) reaching the central cytoplasm of the cell. Our results indicate that, although single-channel Ca(2+) transients could increase SR Ca(2+) to a certain extent, SR Ca(2+) uptake is not rapid enough to greatly affect the magnitude of these transients or their spread to the central cytoplasm unless the Ca(2+) 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 Ca(2+) pumps or phospholamban between the peripheral and central SR in smooth muscle cells.
质膜与近膜肌浆网（SR）之间的微环境可能在平滑肌细胞的Ca(2+)调节中发挥重要作用。我们使用了Ca(2+)扩散和调节的三维数学模型以及对分离的平滑肌细胞中SR Ca(2+)摄取和SR分布的实验测量，来预测单个质膜Ca(2+)通道开放后近膜SR加载Ca(2+)的程度。我们还模拟了SR摄取对以下方面的影响：1）近膜空间中的单通道Ca(2+)瞬变；2）该空间中Ca(2+)与Ca(2+)缓冲剂的结合；3）到达细胞中央细胞质的Ca(2+)量。我们的结果表明，虽然单通道Ca(2+)瞬变可以在一定程度上增加SR Ca(2+)，但SR Ca(2+)摄取速度不够快，不足以极大地影响这些瞬变的幅度或它们向中央细胞质的扩散，除非外周SR的Ca(2+)摄取速率比我们实验得出的平均速率高一个数量级。然而，免疫荧光成像并未揭示平滑肌细胞外周和中央SR之间SR Ca(2+)泵或受磷蛋白密度的明显差异。
