Role of the sarcolemmal adenosine triphosphate-sensitive potassium channel in hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility

Background. Hyperkalemic cardioplegia (Plegisol) has been shown to result in myocyte swelling and reduced contractility. We have demonstrated the elimination of these detrimental effects by the addition of an adenosine triphosphate-sensitive K^- (K_ATP) channel opener. To examine whether the mitochondrial or sarcolemmal K_ATP channel might be involved, volume and contractility in isolated myocytes from wild-type mice and mice lacking the sarcolemmal K_ATP channel (Kir6.2-/-) were evaluated. Methods. Myocytes were perfused for 20 minutes each with control 37°C Tyrode's solution, test solution, and then control solution. Test solutions were (n = 10 per group) either 9°C Plegisol or 9°C Plegisol with 100 μmol/L of diazoxide, a putative mitochondrial-specific K _ATP channel opener. Cell volume and contractility were measured by digital video microscopy at baseline and during the test solution and reexposure periods. Results. Myocytes from wild-type mice, perfused with 9°C Plegisol, demonstrated significant cell swelling (11.2% ± 0.4%; p < 0.01) and diminished contractility (32.5% ± 9.6% reduction in percent shortening, 47.2% ± 10.1% reduction in peak velocity of shortening, and 52.0% ± 8.8% reduction in peak velocity of relengthening; p < 0.05) versus baseline. Cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In Kir6.2-/- myocytes, Plegisol caused a greatly reduced level of cell swelling (3.2% ± 0.1%; p < 0.01), and this was unaffected by diazoxide. Contractility was unchanged in Kir6.2-/- myocytes after Plegisol. Conclusions. The sarcolemmal K_ATP channel appears necessary for exaggerated cell swelling and reduced contractility to occur after hyperkalemic cardioplegia in mouse myocytes.