Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts

John C. Quindry, Lindsey Schreiber, Peter Hosick, Jenna Wrieden, J. Megan Irwin, Emily Hoyt

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51 Citations (Scopus)

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 KATP) 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 KATP (5-hydroxydecanoate) or sarc KATP (HMR1098) before IR. Blinded analysis of digital ECG tracings revealed that mito KATP 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 KATP-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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number1
DOIs
StatePublished - 1 Jul 2010

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Anti-Arrhythmia Agents
Reperfusion
Cardiac Arrhythmias
Ischemia
Adenosine Triphosphate
KATP Channels
Sarcolemma
Glutathione Peroxidase
Catalase
Superoxide Dismutase
Oxidation-Reduction
Sprague Dawley Rats
mitochondrial K(ATP) channel
Mitochondria
Electrocardiography
Oxidative Stress
Antioxidants
Pharmacology
Enzymes

Keywords

  • Cardioprotection
  • Ischemia-reperfusion
  • Myocardial
  • Oxidative stress
  • Preconditioning

Cite this

Quindry, John C. ; Schreiber, Lindsey ; Hosick, Peter ; Wrieden, Jenna ; Irwin, J. Megan ; Hoyt, Emily. / Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 299, No. 1.
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Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. / Quindry, John C.; Schreiber, Lindsey; Hosick, Peter; Wrieden, Jenna; Irwin, J. Megan; Hoyt, Emily.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 1, 01.07.2010.

Research output: Contribution to journalArticleResearchpeer-review

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