Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice

Masashi Suzuki, Norihito Sasaki, Takashi Miki, Naoya Sakamoto, Yuki Ohmoto-Sekine, Masaji Tamagawa, Susumu Seino, Eduardo Marbán, Haruaki Nakaya

Research output: Contribution to journalArticle

Abstract

Recently it has been postulated that mitochondrial ATP-sensitive K+ (mitoKATP) channels rather than sarcolemmal KATP (sarcKATP) channels are important as end effectors and/or triggers of ischemic preconditioning (IPC). To define the pathophysiological significance of sarcKATP channels, we conducted functional experiments using Kir6.2-deficient (KO) mice. Metabolic inhibition with glucose-free, dinitrophenol-containing solution activated sarcKATP current and shortened the action potential duration in ventricular cells isolated from wild-type (WT) but not KO mice. MitoKATP channel function was preserved in KO ventricular cells. In anesthetized mice, IPC reduced the infarct size in WT but not KO mice. Following global ischemia/reperfusion, the increase of left ventricular end-diastolic pressure during ischemia was more marked, and the recovery of contractile function was worse, in KO hearts than in WT hearts. Treatment with HMR1098, a sarcKATP channel blocker, but not 5-hydroxydecanoate, a mitoKATP channel blocker, produced a deterioration of contractile function in WT hearts comparable to that of KO hearts. These findings suggest that sarcKATP channels figures prominently in modulating ischemia/reperfusion injury in the mouse. The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcKATP channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalJournal of Clinical Investigation
Volume109
Issue number4
DOIs
Publication statusPublished - 2002

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Suzuki, M., Sasaki, N., Miki, T., Sakamoto, N., Ohmoto-Sekine, Y., Tamagawa, M., ... Nakaya, H. (2002). Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice. Journal of Clinical Investigation, 109(4), 509-516. https://doi.org/10.1172/JCI200214270