The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle

eLife

Roger A Bannister¹  Andrew A Voss²  Steve RA Burke²  Murad Nawaz³  Jessica H Myers³  Chris DuPont³  Mark M Rich³  Xueyong Wang³  Brent D Foy⁴ 

[1] University of Maryland School of Medicine, Departments of Pathology/Biochemistry & Molecular Biology, Baltimore, United States;Wright State University, Department of Biological Sciences, Dayton, United States;Wright State University, Department of Neuroscience, Cell Biology, and Physiology, Dayton, United States;Wright State University, Department of Physics, Dayton, United States;

关键词: skeletal muscle;    action potential;    excitation contraction coupling;    depolarization;    calcium release;   

DOI  :  10.7554/eLife.71588

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown