The effect of inactivation of calcium channels by intracellular Ca2+ ions in the bursting pancreatic beta-cells.

The effect of inactivation of calcium channels by intracellular Ca2+ ions in the bursting pancreatic beta-cells.
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破裂的胰腺 β 细胞中细胞内 Ca2 离子对钙通道失活的影响。

DOI:
10.1007/bf02797114
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发表时间:
1987
期刊:
Cell biophysics
影响因子:
--
通讯作者:
Chay,TR
Chay,TR
中科院分区:
--
文献类型:
--
作者:
Chay,TR

文献摘要

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本文根据最近测定的离子通道特性,建立了一个简单的胰腺β细胞爆发活动的理论模型。该模型包含由细胞内钙离子失活的内向电压激活的钙电流和由膜电位激活的外向K+电流。沟道门打开的概率用玻耳兹曼方程表示。我们的模型适用于ATP可阻断的K+通道被抑制的情况。在这种情况下,葡萄糖被视为细胞内钙离子外流速率的激活剂,因此它的影响等同于tokCa,即外流速率常数。此外,细胞内的H+离子是糖酵解代谢过程的副产物,被视为钙离子的竞争性抑制物。由于H+是一种竞争性抑制物(根据我们的假设),它的影响等同于CaI离解常数Kh的强度。在该模型中,假设在电压门控钙通道的内膜上存在一个钙结合部位。该模型预测,变化的kca可以产生尖峰和爆发式的电模式,而给定的模式可能会产生不同水平的细胞内钙离子,这取决于Kh。换句话说,它预测通过适当控制葡萄糖和pH的浓度,可以将[Ca~(2+)]的水平与电活动分开。这可能解释了Lebrun等人的实验观察。(1985)认为胰岛素的分泌与电活动的爆发无关。
Based on recently determined ionic channel properties, a simple theoretical model for the burst activity of the pancreatic β-cell is formulated in this paper. The model contains an inward voltage-activated Ca2+current which is inactivated by intracellular calcium ions and an outward K+current that is activated by the membrane potential. The probability of opening of the channel gates is represented by Boltzmann equations. Our model is applicable in a regime where an ATP-blockable K+channel is inhibited. In this regime, glucose is treated as an activator for the rate of efflux of intracellular Ca2+ions, and hence its effect is equated tokCa, the efflux rate constant. In addition, intracellular H+ion, which is a byproduct of the glycolytic metabolic process, is treated as a competitive inhibitor for Ca2+ion. Since H+is a competitive inhibitor (according to our assumption), its effect is equated to the strength of the Caidissociation constantKh. In the model, a Ca2+binding site is assumed to exist in the inner membrane of the voltage-gated Ca2+channel. The model predicts that a spike and burst electrical pattern can be generated by varyingkcaand that a given pattern may produce different levels of intracellular Ca2+depending onKh. In other words, it predicts that levels of [Ca2+]ican be separated from the electrical activity by controlling the concentration of glucose and pH appropriately. This may account for the experimental observation of Lebrun et al. (1985) that insulin secretion is not correlated to the burst of electrical activity.