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Role of KATP Channels in Beneficial Effects of Exercise in Ischemic Heart Failure.

Medicine and science in sports and exercise (2015-06-10)
Jasenka Kraljevic, Morten Andre Høydal, Marko Ljubkovic, Jose Bianco Nascimento Moreira, Kari Jørgensen, Henning Ofstad Ness, Fredrik Hjulstad Bækkerud, Zeljko Dujic, Ulrik Wisløff, Jasna Marinovic
ABSTRACT

Exercise training reduces pathological remodeling and improves cardiac function in ischemic heart failure; however, causal mechanisms underlying the cardiac benefits of exercise are poorly understood. Because opening of adenosine triphosphate (ATP)-sensitive K ⁺(KATP) channels protects the heart during myocardial stress, we hypothesized that such a mechanism is responsible for some of the cardiac benefits induced by exercise in postinfarction chronic heart failure (CHF). Left ventricular myocytes were isolated from three groups of rats: Sham, CHF Tr (4 wk after myocardial infarction, rats underwent 8 wk of aerobic interval training 5 d·wk⁻¹) and CHF Sed (rats sedentary for 12 wk after infarction). Cardiomyocyte survival after oxidative stress exposure (200 μM H2O2) and calcium handling (cells loaded with Fura-2 AM and electrically paced at 1 Hz) were assessed in the presence of KATP channel inhibitor glibenclamide. Expression of KATP subunits (SUR2A and Kir6.2) was evaluated using immunoblotting. Exercise improved cardiac function in CHF Tr animals. Cardiomyocytes from CHF Sed rats were more susceptible to oxidative stress-induced cell death than CHF Tr and Sham cardiomyocytes, with glibenclamide completely abolishing the protective effect of exercise. Glibenclamide did not affect cardiomyocyte survival in Sham or CHF Sed rats. In addition, exercise increased the systolic Ca²⁺ transient amplitude and improved diastolic Ca²⁺ removal in CHF Tr cardiomyocytes (compared with CHF Sed); both were significantly attenuated by glibenclamide. Exercise resulted in increased expression of KATP channel subunits in CHF Tr hearts, with more pronounced and significant effect on SUR2A. Our data suggest that KATP channel upregulation induced by chronic exercise likely mediates some of exercise-induced beneficial effects on cardiac function in postischemic heart failure.

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