Abstract 20280: An Open Sarcolemmal Adenosine Triphosphate — Sensitive Potassium Channel is Necessary for Detrimental Myocyte Swelling Secondary to Stress
Introduction: Stress (exposure to hyperkalemic cardioplegia, metabolic inhibition, osmotic) results in significant myocyte swelling and reduced contractility. These detrimental consequences are not observed in mice lacking the Kir6.2 subunit of the sarcolemmal KATP (adenosine triphosphate — sensitive potassium) channel when compared to wild type (WT) mice following exposure to hyperkalemic cardioplegia.
Hypothesis: An open sarcolemmal KATP channel is necessary for detrimental swelling to occur in myocytes exposed to stress.
Methods: High dose KATP channel blockade and genetic deletion (knock out of Kir6.2 subunit) were utilized (N= 4–6 myocytes per group). To evaluate channel blockade, WT mice myocytes were exposed to Tyrode's control (NT) (20 min), stress (hyperkalemic cardioplegia) +/− a KATP channel blocker (glibenclamide, HMR1098, or 5-hydroxydeconoate) (20 min), and NT (20 min). To evaluate genetic deletion, WT and Kir6.2 (−/−) mice myocytes were exposed to NT (20 min), test solution (metabolic inhibition or NT) (20 min), and NT (20 min). Myocyte volume was recorded using image grabbing software. Data are mean ± SEM.
Results: Detrimental myocyte swelling was prevented by high dose sarcolemmal KATP channel blockade (glibenclamide or HMR1098) but not mitochondrial KATP channel blockade (5-hydroxydecanoate) during exposure to hyperkalemic cardioplegia (Figure). Genetic deletion of the sarcolemmal KATP channel prevented significant myocyte swelling in response to metabolic inhibition (WT 3.8%+/− 1.09% vs. Kir6.2 (−/−) −0.4+/− 0.66% volume change during exposure to metabolic inhibition; p<0.05) .
Conclusions: The cardioprotective mechanism of KATP channels is unknown, and KATP channel openers have been found to prevent detrimental myocyte swelling and reduced contractility in response to stress. Paradoxically, these data support a role of the sarcolemmal KATP channel in myocyte volume derangement in response to stress.
- © 2010 by American Heart Association, Inc.