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Overexpression of SUR2A generates a cardiac phenotype resistant to ischemia
Author(s) -
Du Qingyou,
Jovanović Sofija,
Clelland Allyson,
Sukhodub Andrey,
Budas Grant,
Phelan Karen,
Murray-Tait Victoria,
Malone Lorraine,
Joyanmć Aleksandar
Publication year - 2006
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.05-5483com
Subject(s) - sarcolemma , genetically modified mouse , myocyte , transgene , protein subunit , microbiology and biotechnology , biology , western blot , medicine , chemistry , endocrinology , biochemistry , gene
ABSTRACT ATP‐sensitive K + (K ATP ) channels are present in the sarcolemma of cardiac myocytes where they link membrane excitability with the cellular bioen‐ergetic state. These channels are in vivo composed of Kir6.2, a pore‐forming subunit, SUR2A, a regulatory subunit, and at least four accessory proteins. In the present study, real‐time RT‐PCR has demonstrated that of all six sarcolemmal K ATP channel‐forming proteins, SUR2A was probably the least expressed protein. We have generated mice where the SUR2A was under the control of a cytomegalovirus promoter, a promoter that is more efficient than the native promoter. These mice had an increase in SUR2A mRNA/protein levels in the heart whereas levels of mRNAs of other channel‐forming proteins were not affected at all. Imunopre‐cipitation/Western blot and patch clamp electrophysi‐ology has shown an increase in K ATP channel numbers in the sarcolemma of transgenic mice. Cardiomyocytes from transgenic mice responded to hypoxia with shortening of action membrane potential and were significantly more resistant to this insult than cardiomyocytes from the wild‐type. The size of myocardial infarction in response to ischemia‐reperfusion was much smaller in hearts from transgenic mice compared to those in wild‐type. We conclude that overexpression of SUR2A generates cardiac phenotype resistant to hypoxia/isch‐emia/reperfusion injury due at least in part to increase in levels of sarcolemmal K ATP channels.—Du, Q., Jovanovic, S., Clelland, A., Sukhodub, A., Budas, G., Phelan, K., Murray‐Tait, V., Malone, L., Jovanovic, A. Overexpression of sur2a generates cardiac phenotype resistant to ischemia. FASEBJ . 20, 1131–1141 (2006)