Affiliation:
1. From the Division of Cardiothoracic Surgery (A.D.S., A.S.A.-D., R.B.S., J.S.L.), Department of Surgery, and Department of Cell Biology and Physiology (C.G.N.), Washington University School of Medicine, St Louis, MO.
Abstract
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 (sK
ATP
) channel after exposure to hyperkalemic cardioplegia. The hypothesis for this study was that an open sK
ATP
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 sK
ATP
channel in stress-induced myocyte swelling, high-dose pharmacological sK
ATP
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 K
ATP
channel blocker. To evaluate the effects of genetic deletion, wild-type and sK
ATP
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 sK
ATP
channel blockade (glibenclamide or HMR 1098) but not mitochondrial K
ATP
channel blockade (5-hydroxydecanoate) during exposure to hyperkalemic cardioplegia. Genetic deletion of the sK
ATP
channel prevented significant myocyte swelling in response to metabolic inhibition.
Conclusions—
K
ATP
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 sK
ATP
channel activation in myocyte volume derangement in response to stress.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献