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Article
The Role of Action Potential Waveform in Failure of Excitation Contraction Coupling
bioRxiv
  • Xueyong Wang, Wright State University - Main Campus
  • Murad Nawaz, Wright State University
  • Steve R.A. Burke, Wright State University - Main Campus
  • Roger Bannister
  • Brent D. Foy, Wright State University - Main Campus
  • Andrew A. Voss, Wright State University - Main Campus
  • Mark M. Rich, Wright State University - Main Campus
Document Type
Article
Publication Date
6-30-2021
Identifier/URL
96345216 (Orcid)
Abstract

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, ICU 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 range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials (APs) in individual fibers during depolarization revealed that APs do not fail in an all-or-none manner. Simultaneous imaging of Ca2+ transients during depolarization revealed failure over a narrow range of resting potentials. An AP property that closely correlated with the sudden failure of the Ca2+ transient was the integral of AP voltage with respect to time. We hypothesize the close correlation is due to the combined dependence on time and voltage of Ca2+ release from the sarcoplasmic reticulum. The quantitative relationships established between resting potential, APs and Ca2+ transients provide the foundation for future studies of depolarization-induced failure of ECC in diseases such as periodic paralysis.

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Preprint Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.1101/2021.06.29.450361
Citation Information
Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, et al.. "The Role of Action Potential Waveform in Failure of Excitation Contraction Coupling" bioRxiv (2021)
Available at: http://works.bepress.com/mark_rich/101/