Impaired exercise tolerance and skeletal muscle myopathy in sulfonylurea receptor-2 mutant mice

Douglas Stoller, Peter Pytel, Sophie Katz, Judy U. Earley, Keith Collins, Jamie Metcalfe, Roberto M. Lang, Elizabeth M. McNally

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

By sensing intracellular energy levels, ATP-sensitive potassium (K ATP) channels help regulate vascular tone, glucose metabolism, and cardioprotection. SUR2 mutant mice lack full-length KATP channels in striated and smooth muscle and display a complex phenotype of hypertension and coronary vasospasm. SUR2 mutant mice also display baseline cardioprotection and can withstand acute sympathetic stress better than normal mice. We now studied response to a form of chronic stress, namely that induced by 4 wk of daily exercise on SUR2 mutant mice. Control mice increased exercise capacity by 400% over the training period, while SUR2 mutant mice showed little increase in exercise capacity. Unexercised SUR2 mutant showed necrotic and regenerating fibers in multiple muscle skeletal muscles, including quadriceps, tibialis anterior, and diaphragm muscles. Unlike exercised control animals, SUR2 mutant mice did not lose weight, presumably due to less overall exertion. Unexercised SUR2 mutant mice showed a trend of mildly reduced cardiac function, measured by fractional shortening, (46 ± 4% vs. 57 ± 7% for SUR2 mutant and control, respectively), and this decrease was not exacerbated by chronic exercise exposure. Despite an improved response to acute sympathetic stress and baseline cardioprotection, exercise intolerance results from lack of SUR2 K ATP channels in mice.

Original languageEnglish (US)
Pages (from-to)R1144-R1153
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume297
Issue number4
DOIs
StatePublished - Oct 2009

Keywords

  • Exercise intolerance
  • K channel
  • SUR2
  • Skeletal myopathy
  • Sulfonylurea receptor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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