Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

Ana Sierra; Ekaterina Subbotina; Zhiyong Zhu; Zhan Gao; Siva Rama Krishna Koganti; William A Coetzee; David J Goldhamer; Denice M Hodgson-Zingman; Leonid V Zingman

doi:10.1016/j.bbrc.2016.01.166

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Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

Journal article

Peer reviewed

Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

Ana Sierra, Ekaterina Subbotina, Zhiyong Zhu, Zhan Gao, Siva Rama Krishna Koganti, William A Coetzee, David J Goldhamer, Denice M Hodgson-Zingman and Leonid V Zingman

Biochemical and biophysical research communications, Vol.471(1), pp.129-134

02/26/2016

DOI: 10.1016/j.bbrc.2016.01.166

PMCID: PMC4815902

PMID: 26828268

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Abstract

Sarcolemmal ATP-sensitive potassium (KATP) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle KATP channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle KATP channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of KATP channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish KATP channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. •ATP-sensitive K+ channels regulate musclin production by skeletal muscles.•Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production.•Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway.•Musclin links adipose mobilization to energy use in KATP channel deficient skeletal muscle.

Action potential

Endurance

Calcium

Natriuretic peptide

Fatty acid

Details

Title: Subtitle: Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin
Creators: Ana Sierra - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Ekaterina Subbotina - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Zhiyong Zhu - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Zhan Gao - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Siva Rama Krishna Koganti - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
William A Coetzee - Department of Pediatrics, NYU School of Medicine, New York, NY 10016, USA
David J Goldhamer - Center for Regenerative Biology, Department of Molecular and Cell Biology, Advanced Technology Laboratory, University of Connecticut, 1392 Storrs Road Unit 4243, Storrs, Connecticut 06269, USA
Denice M Hodgson-Zingman - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Leonid V Zingman - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.471(1), pp.129-134
DOI: 10.1016/j.bbrc.2016.01.166
PMID: 26828268
PMCID: PMC4815902
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: HL113089, DK092412, HL085820, HL126905, AR052777; name: VA Merit Review Program, award: 1I0BX000718
Language: English
Date published: 02/26/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094310602771

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