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具有温度依赖性和失活恢复特性的心脏钠通道马尔可夫模型

Cardiac sodium channel Markov model with temperature dependence and recovery from inactivation.

作者信息

Irvine L A, Jafri M S, Winslow R L

机构信息

Department of Biomedical Engineering, Center for Computational Medicine and Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

出版信息

Biophys J. 1999 Apr;76(4):1868-85. doi: 10.1016/s0006-3495(99)77346-7.

Abstract

A Markov model of the cardiac sodium channel is presented. The model is similar to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an additional open state is added; 2) open-inactivated transitions are made voltage-dependent; and 3) channel rate constants are exponential functions of enthalpy, entropy, and voltage and have explicit temperature dependence. Model parameters are determined using a simulated annealing algorithm to minimize the error between model responses and various experimental data sets. The model reproduces a wide range of experimental data including ionic currents, gating currents, tail currents, steady-state inactivation, recovery from inactivation, and open time distributions over a temperature range of 10 degrees C to 25 degrees C. The model also predicts measures of single channel activity such as first latency, probability of a null sweep, and probability of reopening.

摘要

本文提出了一种心脏钠通道的马尔可夫模型。该模型与Kuo和Bean(1994年,《神经元》,12:819 - 829)开发的CA1海马神经元钠通道模型相似,但有以下修改:1)增加了一个额外的开放状态;2)使开放 - 失活转变依赖于电压;3)通道速率常数是焓、熵和电压的指数函数,并且具有明确的温度依赖性。使用模拟退火算法确定模型参数,以最小化模型响应与各种实验数据集之间的误差。该模型再现了广泛的实验数据,包括离子电流、门控电流、尾电流、稳态失活、失活恢复以及在10摄氏度至25摄氏度温度范围内的开放时间分布。该模型还预测了单通道活动的指标,如首次潜伏期、零扫描概率和重新开放概率。

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