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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/4/R1144    most recent 00081.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Stoller, D. Articles by McNally, E. M. PubMed PubMed Citation Articles by Stoller, D. Articles by McNally, E. M.

Articles

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

¹Committee on Cellular and Molecular Physiology, ²Department of Pathology, ³Department of Medicine, and ⁴Department of Human Genetics, The University of Chicago, Chicago, Illinois

Submitted February 6, 2009 ; accepted in final form August 10, 2009

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 K_ATP 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.

K_ATP channel; sulfonylurea receptor; SUR2; skeletal myopathy; exercise intolerance