Sherman A, Keizer J, Rinzel J
National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases, Mathematical Research Branch, Bethesda, Maryland 20892.
Biophys J. 1990 Oct;58(4):985-95. doi: 10.1016/S0006-3495(90)82443-7.
The "shell" model for Ca2(+)-inactivation of Ca2+ channels is based on the accumulation of Ca2+ in a macroscopic shell beneath the plasma membrane. The shell is filled by Ca2+ entering through open channels, with the elevated Ca2+ concentration inactivating both open and closed channels at a rate determined by how fast the shell is filled. In cells with low channel density, the high concentration Ca2+ "shell" degenerates into a collection of nonoverlapping "domains" localized near open channels. These domains form rapidly when channels open and disappear rapidly when channels close. We use this idea to develop a "domain" model for Ca2(+)-inactivation of Ca2+ channels. In this model the kinetics of formation of an inactivated state resulting from Ca2+ binding to open channels determines the inactivation rate, a mechanism identical with that which explains single-channel recordings on rabbit-mesenteric artery Ca2+ channels (Huang Y., J. M. Quayle, J. F. Worley, N. B. Standen, and M. T. Nelson. 1989. Biophys. J. 56:1023-1028). We show that the model correctly predicts five important features of the whole-cell Ca2(+)-inactivation for mouse pancreatic beta-cells (Plants, T. D. 1988. J. Physiol. 404:731-747) and that Ca2(+)-inactivation has only minor effects on the bursting electrical activity of these cells.
钙离子通道钙（2+）失活的“壳”模型基于质膜下方宏观壳层中钙离子的积累。该壳层由通过开放通道进入的钙离子填充，升高的钙离子浓度以壳层填充速度决定的速率使开放和关闭的通道失活。在通道密度低的细胞中，高浓度的钙离子“壳”退化为位于开放通道附近的不重叠“区域”的集合。这些区域在通道开放时迅速形成，在通道关闭时迅速消失。我们利用这一概念开发了一种钙离子通道钙（2+）失活的“区域”模型。在该模型中，钙离子与开放通道结合导致失活状态形成的动力学决定了失活速率，这一机制与解释兔肠系膜动脉钙离子通道单通道记录的机制相同（黄Y.、J.M.奎尔、J.F.沃利、N.B.斯坦登和M.T.纳尔逊。1989年。生物物理学杂志。56:1023 - 1028）。我们表明，该模型正确预测了小鼠胰腺β细胞全细胞钙（2+）失活的五个重要特征（普兰茨，T.D. 1988年。生理学杂志。404:731 - 747），并且钙（2+）失活对这些细胞的爆发性电活动只有轻微影响。
