Impaired exercise tolerance and skeletal muscle myopathy in sulfonylurea receptor-2 mutant mice.
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.
Stoller
Douglas
D
Committee on Cellular and Molecular Physiology, The University of Chicago, Chicago, Illinois 60637, USA.
Pytel
Peter
P
Katz
Sophie
S
Earley
Judy U
JU
Collins
Keith
K
Metcalfe
Jamie
J
Lang
Roberto M
RM
McNally
Elizabeth M
EM
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017079:Exercise Tolerance / Q000235:genetics; D005260:Female; D005838:Genotype; D006706:Homeostasis; D054086:KATP Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009200:Myocardial Contraction; D009336:Necrosis; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D012508:Sarcolemma / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D064233:Sulfonylurea Receptors; D013997:Time Factors; D015431:Weight Loss
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors
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