title: Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts.
abstract: The mechanisms responsible for anti-arrhythmic protection during ischemia-reperfusion (IR) in exercised hearts are not fully understood. The purpose of this investigation was to examine whether the ATP-sensitive potassium channels in the mitochondria (mito K(ATP)) and sarcolemma (sarc K(ATP)) provide anti-arrhythmic protection in exercised hearts during IR. Male Sprague-Dawley rats were randomly assigned to cardioprotective treadmill exercise or sedentary conditions before IR (I = 20 min, R = 30 min) in vivo. Subsets of exercised animals received pharmacological inhibitors for mito K(ATP) (5-hydroxydecanoate) or sarc K(ATP) (HMR1098) before IR. Blinded analysis of digital ECG tracings revealed that mito K(ATP) inhibition blunted the anti-arrhythmic effects of exercise, while sarc K(ATP) inhibition did not. Endogenous antioxidant enzyme activities for total, CuZn, and Mn superoxide dismutase, catalase, and glutathione peroxidase from ischemic and perfused ventricular tissue were not mitigated by IR, although oxidative stress was elevated in sedentary and mito K(ATP)-inhibited hearts from exercised animals. These findings suggest that the mito K(ATP) channel provides anti-arrhythmic protection as part of exercise-mediated cardioprotection against IR. Furthermore, these data suggest that the observed anti-arrhythmic protection may be associated with preservation of redox balance in exercised hearts.
authors.affiliation: Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, AL 36849, USA. jcq0001@auburn.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Quindry
authors.forename: Lindsey
authors.initials: L
authors.lastname: Schreiber
authors.forename: Peter
authors.initials: P
authors.lastname: Hosick
authors.forename: Jenna
authors.initials: J
authors.lastname: Wrieden
authors.forename: J Megan
authors.initials: JM
authors.lastname: Irwin
authors.forename: Emily
authors.initials: E
authors.lastname: Hoyt
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001549:Benzamides / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005979:Glutathione Peroxidase / Q000378:metabolism; D006880:Hydroxy Acids / Q000494:pharmacology*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D005082:Physical Exertion; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; C410297:HMR 1098; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase