Li Y X, Stojilković S S, Keizer J, Rinzel J
Mathematical Research Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biophys J. 1997 Mar;72(3):1080-91. doi: 10.1016/S0006-3495(97)78758-7.
Inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ mobilization leads to depletion of the endoplasmic reticulum (ER) and an increase in Ca2+ entry. We show here for the gonadotroph, an excitable endocrine cell, that sensing of ER Ca2+ content can occur without the Ca2+ release-activated Ca2+ current (Icrac), but rather through the coupling of IP3-induced Ca2+ oscillations to plasma membrane voltage spikes that gate Ca2+ entry. Thus we demonstrate that capacitative Ca2+ entry is accomplished through Ca(2+)-controlled Ca2+ entry. We develop a comprehensive model, with parameter values constrained by available experimental data, to simulate the spatiotemporal behavior of agonist-induced Ca2+ signals in both the cytosol and ER lumen of gonadotrophs. The model combines two previously developed models, one for ER-mediated Ca2+ oscillations and another for plasma membrane potential-driven Ca2+ oscillations. Simulations show agreement with existing experimental records of store content, cytosolic Ca2+ concentration ([Ca2+]i), and electrical activity, and make a variety of new, experimentally testable predictions. In particular, computations with the model suggest that [Ca2+]i in the vicinity of the plasma membrane acts as a messenger for ER content via Ca(2+)-activated K+ channels and Ca2+ pumps in the plasma membrane. We conclude that, in excitable cells that do not express Icrac, [Ca2+]i profiles provide a sensitive mechanism for regulating net calcium flux through the plasma membrane during both store depletion and refilling.
肌醇1,4,5 -三磷酸（IP3）诱导的Ca2+动员导致内质网（ER）中Ca2+的耗尽以及Ca2+内流增加。我们在此表明，对于促性腺激素细胞（一种可兴奋的内分泌细胞），内质网Ca2+含量的感知可以在没有Ca2+释放激活的Ca2+电流（Icrac）的情况下发生，而是通过将IP3诱导的Ca2+振荡与控制Ca2+内流的质膜电压尖峰耦合来实现。因此，我们证明了容量性Ca2+内流是通过Ca(2+)-控制的Ca2+内流来完成的。我们开发了一个综合模型，其参数值由可用的实验数据约束，以模拟激动剂诱导的Ca2+信号在促性腺激素细胞的细胞质和内质网腔中的时空行为。该模型结合了两个先前开发的模型，一个用于内质网介导的Ca2+振荡，另一个用于质膜电位驱动的Ca2+振荡。模拟结果与现有的关于储存库含量、细胞质Ca2+浓度（[Ca2+]i）和电活动的实验记录一致，并做出了各种新的、可通过实验验证的预测。特别是，用该模型进行的计算表明，质膜附近的[Ca2+]i通过质膜中的Ca(2+)-激活K+通道和Ca2+泵作为内质网含量的信使。我们得出结论，在不表达Icrac的可兴奋细胞中，[Ca2+]i分布提供了一种敏感机制，用于在储存库耗尽和重新填充期间调节通过质膜的净钙通量。
