Korngreen A, Gold'shtein V, Priel Z
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Biophys J. 1997 Aug;73(2):659-73. doi: 10.1016/S0006-3495(97)78101-3.
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.
在许多非电兴奋性细胞中，从内部储存库释放钙之后会进入一个慢得多的阶段，在此阶段细胞内钙浓度会逐渐降低至高于刺激前浓度的一个稳定值。已证明这种升高的钙平台是钙内流的结果。本研究提出的模型描述了一个系统，该系统由一个细胞质钙储存库和一个质膜钙通道组成，二者均可被膜受体激活；一个快速的细胞质钙缓冲剂；以及钙储存库和细胞膜中的钙泵。由于跨储存库膜的钙通量非常大，模型数值评估存在固有困难，通过将钙释放的快速过程与跨质膜钙循环的较慢过程进行解析分离得以克服。这使得能够模拟出与实验观察到的类似的逼真双相钙瞬变。该模型预测：1）跨质膜钙循环速率与钙衰减速率之间存在强相关性；2）细胞质钙浓度的最大升高水平、升高的钙平台水平以及钙衰减速率依赖于细胞兴奋水平。利用该模型，我们在几种实验条件下模拟了从浴液中洗脱激动剂以及用药理剂（如毒胡萝卜素）耗尽钙储存库的情况。
