Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart

Shoji Sanada, Masafumi Kitakaze, Hiroshi Asanuma, Kengo Harada, Hisakazu Ogita, Koichi Node, Seiji Takashima, Yasuhiko Sakata, Masanori Asakura, Yoshiro Shinozaki, Hidezo Mori, Tsunehiko Kuzuya, Masatsugu Hori

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

We tested whether mitochondrial or sarcolemmal ATP-sensitive K′ (KATP) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific KATP channel openers) markedly limited infarct size (6.3 ± 1.2, 8.9 ± 1.9, and 7.2 ± 1.6%, respectively) compared with the control group (40.9 ± 4.1%). A selective mitochondrial KATP channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 ± 3.8, 25.1 ± 4.6, and 19.8 ± 5.2%, respectively). A nonspecific KATP channel blocker, glibenclamide, completely abolished the effect of IP (38.5 ± 6.2%). Intracoronary or intravenous administration of a mitochondria-selective KATP channel opener, diazoxide, at >100 μmol/l could only partially decrease infarct size (19.5 ± 4.3 and 20.1 ± 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal KATP channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Original languageEnglish
Pages (from-to)H256-H263
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number1 49-1
DOIs
Publication statusPublished - 2001

Keywords

  • 5-hydroxydecanoate
  • Diazoxide
  • Infarct size

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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