Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads

Zhiyong Zhu, Ana Sierra, Colin M.L. Burnett, Biyi Chen, Ekaterina Subbotina, Siva Rama Krishna Koganti, Zhan Gao, Yuejin Wu, Mark E. Anderson, Long Sheng Song, David J. Goldhamer, William A. Coetzee, Denice M. Hodgson-Zingman, Leonid V. Zingman

Research output: Contribution to journalArticle

Abstract

ATP-sensitive potassium (KATP) channels have the unique ability to adjust membrane excitability and functions in accordance with the metabolic status of the cell. Skeletal muscles are primary sites of activity-related energy consumption and have KATP channels expressed in very high density. Previously, we demonstrated that transgenic mice with skeletal muscle-specific disruption of KATP channel function consume more energy than wild-type littermates. However, how KATP channel activation modulates skeletal muscle resting and action potentials under physiological conditions, particularly low-intensity workloads, and how this can be translated to muscle energy expenditure are yet to be determined. Here, we developed a technique that allows evaluation of skeletal muscle excitability in situ, with minimal disruption of the physiological environment. Isometric twitching of the tibialis anterior muscle at 1 Hz was used as a model of low-intensity physical activity in mice with normal and genetically disrupted KATP channel function. This workload was sufficient to induce KATP channel opening, resulting in membrane hyperpolarization as well as reduction in action potential overshoot and duration. Loss of KATP channel function resulted in increased calcium release and aggravated activity-induced heat production. Thus, this study identifies low-intensity workload as a trigger for opening skeletal muscle KATP channels and establishes that this coupling is important for regulation of myocyte function and thermogenesis. These mechanisms may provide a foundation for novel strategies to combat metabolic derangements when energy conservation or dissipation is required.

Original languageEnglish (US)
Pages (from-to)119-134
Number of pages16
JournalJournal of General Physiology
Volume143
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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    Zhu, Z., Sierra, A., Burnett, C. M. L., Chen, B., Subbotina, E., Koganti, S. R. K., Gao, Z., Wu, Y., Anderson, M. E., Song, L. S., Goldhamer, D. J., Coetzee, W. A., Hodgson-Zingman, D. M., & Zingman, L. V. (2014). Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads. Journal of General Physiology, 143(1), 119-134. https://doi.org/10.1085/jgp.201311063