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K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

Lawrence, KM; Chanalaris, A; Scarabelli, T; Hubank, M; Pasini, E; Townsend, PA; Comini, L; ... Latchman, DS; + view all (2002) K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect. CIRCULATION , 106 (12) 1556 - 1562. 10.1161/01.CIR.0000028424.02525.AE. Green open access

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Abstract

Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent.

Type: Article
Title: K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/01.CIR.0000028424.02525.AE
Keywords: potassium channel, urocortin, ischemia, reperfusion, PROTEIN-KINASE-C, CARDIAC MYOCYTES, DEPENDENT PATHWAY, INJURY, REOXYGENATION, CARDIOTROPHIN-1, MITOCHONDRIA, ACTIVATION, INFARCTION, ISCHEMIA
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
URI: https://discovery.ucl.ac.uk/id/eprint/8500
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