Background-Stress (exposure to hyperkalemic cardioplegia, metabolic inhibition, or osmotic) results in significant myocyte swelling and reduced contractility. In contrast to wild-type mice, these detrimental consequences are not observed in mice lacking the Kir6.2 subunit of the sarcolemmal ATP-sensitive potassium (sKATP) channel after exposure to hyperkalemic cardioplegia. The hypothesis for this study was that an open sKATP channel (Kir6.2 and SUR2A subunits) is necessary for detrimental myocyte swelling to occur in response to stress. Methods and Results-To investigate the role of the sKATP channel in stress-induced myocyte swelling, high-dose pharmacological sKATP channel blockade and genetic deletion (knockout of Kir6.2 subunit) were used. Myocytes were exposed sequentially to Tyrode control (20 minutes), test (stress) solution (20 minutes), and Tyrode control (20 minutes). To evaluate pharmacological channel blockade, myocytes were exposed to hyperkalemic cardioplegia (stress) with and without a KATP channel blocker. To evaluate the effects of genetic deletion, wild-type and sKATP knockout [Kir6.2(-/-)] myocytes were exposed to metabolic inhibition (stress). Myocyte volume was recorded using image-grabbing software. Detrimental myocyte swelling was prevented by high-dose sKATP channel blockade (glibenclamide or HMR 1098) but not mitochondrial KATP channel blockade (5-hydroxydecanoate) during exposure to hyperkalemic cardioplegia. Genetic deletion of the sKATP channel prevented significant myocyte swelling in response to metabolic inhibition. Conclusions-KATP channel openers prevent detrimental myocyte swelling and reduce contractility in response to stress through an unknown mechanism. Paradoxically, the present data support a role for sKATP channel activation in myocyte volume derangement in response to stress.
- heart arrest induced
- muscle cells