KATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

K. M. Lawrence, A. Chanalaris, T. Scarabelli, M. Hubank, E. Pasini, P. A. Townsend, L. Comini, R. Ferrari, A. Tinker, A. Stephanou, R. A. Knight, D. S. Latchman

Research output: Contribution to journalArticle

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 gene 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 KATP 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 KATP channel subunit induced by a cardioprotective agent and demonstrates that KATP channel opening is essential for the effect of this novel cardioprotective agent.

Original languageEnglish
Pages (from-to)1556-1562
Number of pages7
JournalCirculation
Volume106
Issue number12
DOIs
Publication statusPublished - Sep 17 2002

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Keywords

  • Ischemia
  • Potassium channel
  • Reperfusion
  • Urocortin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Lawrence, K. M., Chanalaris, A., Scarabelli, T., Hubank, M., Pasini, E., Townsend, P. A., Comini, L., Ferrari, R., Tinker, A., Stephanou, A., Knight, R. A., & Latchman, D. S. (2002). KATP channel gene expression is induced by urocortin and mediates its cardioprotective effect. Circulation, 106(12), 1556-1562. https://doi.org/10.1161/01.CIR.0000028424.02525.AE