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Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial K ATP channels during metabolic inhibition and recovery
Author(s) -
Light Peter E.,
Kanji Hussein D.,
Fox Jocelyn E. Manning,
French Robert J.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0188com
Subject(s) - protein kinase c , adenosine , activator (genetics) , chemistry , ischemic preconditioning , calcium , calcium in biology , myocyte , microbiology and biotechnology , pharmacology , adenosine receptor antagonist , medicine , endocrinology , biology , biochemistry , intracellular , receptor , adenosine receptor , kinase , ischemia , agonist
ABSTRACT The protective roles of sarcolemmal (sarc) and mitochondrial (mito)K ATP channels are un‐clear despite their apparent importance to ischemic preconditioning. We examined these roles by monitoring intracellular calcium ([Ca] int ), using fura‐2 and fluo‐3, in enzymatically isolated rat right ventricular myocytes. Myocyte mortality, estimated using a trypan blue assay, changed approximately in parallel with changes in [Ca] int . Chemically induced hypoxia (CIH), induced by application of cyanide and 2‐deoxy‐glucose, caused a steady rise in [Ca] int . Calcium increased more rapidly on ‘reoxygenation’ by return to control solutions. The protein kinase C (PKC) activator PMA abolished both phases of calcium increase. The mito K ATP channel‐selective blocker 5‐hydroxydecanoate partially prevented the PMA‐induced protection during CIH, but not during reoxygenation. In contrast, HMR 1098, a sarc K ATP channel‐selective blocker, abolished protection only during the reoxygenation. Adenosine (A 1 ) receptor activation prevented or reduced increases in [Ca] int and improved cell viability via a PKC and mito / sarc K ATP channel‐dependent mechanism. PKC‐dependent protection against cytoplasmic calcium increases was also observed in a human cell line (tsA201) transiently expressing sarc K ATP channels. Protection was abolished only during the reoxygenation phase by the amino acid substitution (T180A) in the pore‐forming Kir6.2 subunit, a mutation previously shown to prevent PKC‐dependent modulation. Our data suggest that sarc and mito K ATP channel populations play distinct protective roles, triggered by PKC and/or adenosine, during chemically induced hypoxia/reoxygenation.—Light, P. E., Kanji, H. D., Manning Fox, J. E., French, R. J. Distinct myoprotective roles of cardiac sarcolem‐mal and mitochondrial K ATP channels during metabolic inhibition and recovery. FASEB J. 15, 2586–2594 (2001)