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 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.
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 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.
Authors: Seán P Barry; Kevin M Lawrence; James McCormick; Surinder M Soond; Mike Hubank; Simon Eaton; Ahila Sivarajah; Tiziano M Scarabelli; Richard A Knight; Christoph Thiemermann; David S Latchman; Paul A Townsend; Anastasis Stephanou Journal: J Mol Endocrinol Date: 2010-05-25 Impact factor: 5.098
Authors: Yuanjing Li; Ming Cai; Li Cao; Xing Qin; Tiantian Zheng; Xiaohua Xu; Taylor M Sandvick; Kirk Hutchinson; Loren E Wold; Keli Hu; Qinghua Sun; D Paul Thomas; Jun Ren; Guanglong He Journal: PLoS One Date: 2014-12-04 Impact factor: 3.240
Authors: Carol Chen-Scarabelli; Louis Saravolatz Ii; Roy McCaukey; Gabriele Scarabelli; Justin Di Rezze; Bibhu Mohanty; Sean Barry; David Latchman; Vassilis Georgiadis; James McCormick; Louis Saravolatz; Richard Knight; Giuseppe Faggian; Jagat Narula; Anastasis Stephanou; Tiziano M Scarabelli Journal: JAKSTAT Date: 2013-05-07
Authors: Paul A Townsend; Sean M Davidson; Samantha J Clarke; Igor Khaliulin; Christopher J Carroll; Tiziano M Scarabelli; Richard A Knight; Anastasis Stephanou; David S Latchman; Andrew P Halestrap Journal: Am J Physiol Heart Circ Physiol Date: 2007-05-04 Impact factor: 4.733