The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle.
The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle.
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DOI：
10.7554/elife.71588
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发表时间：
2022-01-05
期刊：
影响因子：
7.7
通讯作者：
Rich MM
中科院分区：
文献类型：
--
作者：
Wang X;Nawaz M;DuPont C;Myers JH;Burke SR;Bannister RA;Foy BD;Voss AA;Rich MM
兴奋-收缩耦合（ECC）是指肌肉的电兴奋转化为产生力的过程。骨骼肌静息电位去极化有助于周期性瘫痪、重症监护病房获得性虚弱和剧烈运动时可能出现的肌肉疲劳等疾病的ECC失败。当细胞外K+升高使静息电位去极化时，在一个狭窄的静息电位范围内突然发生ECC失效。Ca2+瞬态的同时成像和动作电位（APs）的记录表明，当APs在负电位大于-30mV时达到峰值时，不能产生Ca2+瞬态。与Ca2+瞬态失效密切相关的AP特性是AP电压相对于时间的积分。电极间隔1.6mm同时记录Ca2+瞬态和AP，发现AP峰值低于-21mV时AP传导失败。我们假设AP的传播和Ca2+瞬态的产生是由不同的AP特性控制的：AP传导是由AP峰控制的，而肌浆网Ca2+释放是由AP积分控制的。不同的AP性质可能决定不同的ECC步骤的原因是所涉及的离子通道动力学。控制传播的Na通道具有快速动力学，对AP宽度（因此对AP积分）不敏感，而Ca2+释放受Cav1.1通道的门控电荷运动控制，其具有较慢的动力学，因此Ca2+释放对AP积分敏感。静息电位、AP性质、AP传导和Ca2+瞬态之间的定量关系为静息电位去极化诱导ECC失效的进一步研究奠定了基础。
Excitation-contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, intensive care unit acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a narrow range of resting potentials. Simultaneous imaging of Ca2+ transients and recording of action potentials (APs) demonstrated failure to generate Ca2+ transients when APs peaked at potentials more negative than –30mV. An AP property that closely correlated with failure of the Ca2+ transient was the integral of AP voltage with respect to time. Simultaneous recording of Ca2+ transients and APs with electrodes separated by 1.6mm revealed AP conduction fails when APs peak below –21mV. We hypothesize propagation of APs and generation of Ca2+ transients are governed by distinct AP properties: AP conduction is governed by AP peak, whereas Ca2+ release from the sarcoplasmic reticulum is governed by AP integral. The reason distinct AP properties may govern distinct steps of ECC is the kinetics of the ion channels involved. Na channels, which govern propagation, have rapid kinetics and are insensitive to AP width (and thus AP integral) whereas Ca2+ release is governed by gating charge movement of Cav1.1 channels, which have slower kinetics such that Ca2+ release is sensitive to AP integral. The quantitative relationships established between resting potential, AP properties, AP conduction and Ca2+ transients provide the foundation for future studies of failure of ECC induced by depolarization of the resting potential.