Infection with AV-SUR2A protects H9C2 cells against metabolic stress: A mechanism of SUR2A-mediated cytoprotection independent from the K-ATP channel activity

Qingyou Du, Sofija Jovanovic, Andriy Sukhodub, Aleksandar Jovanovic (Lead / Corresponding author)

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    26 Citations (Scopus)

    Abstract

    Transgenic mice overexpressing SUR2A, a subunit of ATP-sensitive K+ (K-ATP) channels, acquire resistance to myocardial ischaemia. However, the mechanism of SUR2A-mediated cytoprotection is yet to be fully understood. Adenoviral SUR2A construct (AV-SUR2A) increased SUR2A expression, number of K-ATP channels and subsarcolemmal ATP in glycolysis-sensitive manner in H9C2 cells. It also increased K+ current in response to chemical hypoxia, partially preserved subsarcolemmal ATP and increased cell survival. Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K+ conductance, abolished the effect of SUR2A on K+ current, did not affect SUR2A-induced increase in subsarcolemmal ATP and partially inhibited SUR2A-mediated cytoprotection. Infection with 193gly-M-LDH, an inactive mutant of muscle lactate dehydrogenase, abolished the effect of SUR2A on K+ current, subsarcolemmal ATP and cell survival: the effect of 193gly-M-LDH on cell survival was significantly more pronounced than those of Kir6.2AFA. We conclude that AV-SUR2A increases resistance to metabolic stress in H9C2 cells by increasing the number of sarcolemmal K-ATP channels and subsarcolemmal ATP. (C) 2010 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)405-415
    Number of pages11
    JournalBiochimica et Biophysica Acta. Molecular Cell Research
    Volume1803
    Issue number3
    DOIs
    Publication statusPublished - Mar 2010

    Keywords

    • SUR2A
    • ATP
    • K-ATP channel
    • Cardioprotection
    • Ischaemia
    • Heart
    • SENSITIVE POTASSIUM CHANNELS
    • PREVENTS MEMBRANE DEPOLARIZATION
    • CHEMICAL HYPOXIA-REOXYGENATION
    • RABBIT VENTRICULAR MYOCYTES
    • INTRACELLULAR PH
    • GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
    • HEART
    • CARDIOMYOCYTES
    • INHIBITION
    • KINASE

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