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非失活钠通道对可兴奋细胞电行为影响的计算机模拟。

Computer simulations of the effect of non-inactivating sodium channels on the electric behavior of excitable cells.

作者信息

Steinberg I Z

机构信息

Chemical Physics Department, Weizmann Institute of Science, Rehovot, Israel.

出版信息

J Theor Biol. 1988 Jul 21;133(2):193-214. doi: 10.1016/s0022-5193(88)80005-5.

Abstract

Non-inactivating sodium channels have been discovered in various cell types. Additionally, normal voltage-gated sodium channels can be induced to lose their ability to inactivate by treatment with proteolytic enzymes, with certain chemical reagents, or with toxins. The presence of non-inactivating sodium channels in the outer membrane of a cell is expected to profoundly modify the electrical properties of the cell, because the electrical depolarization of the cell and the opening of these channels reciprocally reinforce each other without intrinsic control. The normal resting state may thus be destabilized and a new resting state at depolarized resting potentials may become possible. In this study, computer simulations were carried out to systematically explore the patterns of behavior of excitable cells which have non-inactivating sodium channels in their plasma membrane. The cells were assumed to be space clamped and the relevant Hodgkin and Huxley equations were assumed to describe the electrical behavior of the cells, except that some or all of the sodium channels could not inactivate. The sodium currents were thus represented by the sum of two terms: FI.gNa.m3.h.(V-ENa) + (1-FI).gNa.m3(V-ENa), where FI(0 less than or equal to FI less than or equal to 1) is the fraction of sodium channels which inactivate normally, and the other symbols have their usual significance. The behavior of non-inactivating sodium channels created by pronase treatment or reaction with chemical reagents was found to conform with that predicted by the second term in this expression. The simulations thus quantitatively apply to excitable cells thus treated, but may serve additionally to qualitatively illustrate patterns of electrical activity induced by non-inactivating sodium channels also in other cases. A variety of possible types of electrical behavior was obtained: Normal behavior, including capability of firing action potentials, requires values of FI which are not far from unity, the permissible range depending on the fully activated potassium ion conductance, gK. Bistability, at which the cell may exist in one of two stable states of different resting potential, occurs when the value of FI is lowered. Transitions from the polarized to the depolarized resting states, and vice versa, may be brought about by depolarizing and hyperpolarizing triggers, respectively. Such behavior is like that of memory storage devices. Monostability at depolarized potentials is favored by low FI values and can occur if gK is less than the Hodgkin and Huxley value.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

在各种细胞类型中都发现了非失活钠通道。此外,正常的电压门控钠通道可以通过用蛋白水解酶、某些化学试剂或毒素处理而失去其失活能力。细胞外膜中存在非失活钠通道预计会深刻改变细胞的电特性,因为细胞的电去极化和这些通道的开放相互加强,且没有内在控制。因此,正常的静息状态可能会变得不稳定,而去极化静息电位下的新静息状态可能成为可能。在这项研究中,进行了计算机模拟,以系统地探索质膜中具有非失活钠通道的可兴奋细胞的行为模式。假设细胞处于空间钳制状态,并假设相关的霍奇金和赫胥黎方程描述细胞的电行为,只是部分或所有钠通道不能失活。因此,钠电流由两项之和表示:FI·gNa·m³·h·(V - ENa) + (1 - FI)·gNa·m³(V - ENa),其中FI(0≤FI≤1)是正常失活的钠通道的比例,其他符号具有其通常的意义。发现由链霉蛋白酶处理或与化学试剂反应产生的非失活钠通道的行为与该表达式中的第二项预测的行为一致。因此,这些模拟定量适用于经过如此处理的可兴奋细胞,但也可额外用于定性说明在其他情况下由非失活钠通道诱导的电活动模式。获得了各种可能的电行为类型:正常行为,包括产生动作电位的能力,需要FI值接近1,允许范围取决于完全激活的钾离子电导gK。当FI值降低时,会出现双稳态,此时细胞可能存在于两种不同静息电位的稳定状态之一。从极化静息状态到去极化静息状态的转变,反之亦然,可分别由去极化和超极化触发引起。这种行为类似于记忆存储设备的行为。低FI值有利于去极化电位下的单稳态,如果gK小于霍奇金和赫胥黎值,则可能发生单稳态。(摘要截断于400字)

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