Journal article
Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads
The Journal of general physiology, Vol.143(1), pp.119-134
01/2014
DOI: 10.1085/jgp.201311063
PMCID: PMC3874572
PMID: 24344248
Abstract
ATP-sensitive potassium (K
ATP
) 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 K
ATP
channels expressed in very high density. Previously, we demonstrated that transgenic mice with skeletal muscle–specific disruption of K
ATP
channel function consume more energy than wild-type littermates. However, how K
ATP
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 K
ATP
channel function. This workload was sufficient to induce K
ATP
channel opening, resulting in membrane hyperpolarization as well as reduction in action potential overshoot and duration. Loss of K
ATP
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 K
ATP
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.
Details
- Title: Subtitle
- Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads
- Creators
- Zhiyong Zhu - Department of Internal MedicineAna Sierra - Department of Internal MedicineColin M.-L Burnett - Department of Internal MedicineBiyi Chen - Department of Internal MedicineEkaterina Subbotina - Department of Internal MedicineSiva Rama Krishna Koganti - Department of Internal MedicineZhan Gao - Department of Internal MedicineYuejin Wu - Department of Internal MedicineMark E Anderson - Department of Internal MedicineLong-Sheng Song - Department of Internal MedicineDavid J Goldhamer - Center for Regenerative BiologyWilliam A Coetzee - Department of Pediatrics, New York University School of Medicine, New York, NY 10016Denice M Hodgson-Zingman - Department of Internal MedicineLeonid V Zingman - Department of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of general physiology, Vol.143(1), pp.119-134
- DOI
- 10.1085/jgp.201311063
- PMID
- 24344248
- PMCID
- PMC3874572
- NLM abbreviation
- J Gen Physiol
- ISSN
- 0022-1295
- eISSN
- 1540-7748
- Publisher
- The Rockefeller University Press
- Alternative title
- IKATP modulates muscle function and energetics
- Language
- English
- Date published
- 01/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094218302771
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