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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)129-134
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 26 Feb 2016
Externally publishedYes


  • Action potential
  • Calcium
  • Endurance
  • Fatty acid
  • Natriuretic peptide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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