CFTR Cl⁻チャネル活性化によるin vivo心筋虚血傷害の防御

抄録

Since it is known that molecular and functional expression of CFTR on the plasma membrane is enhanced under glucose-free hypoxic conditions in neonatal rat ventricular myocytes (Jpn J Physiol 53, 357, 2003), there is a possibility that the CFTR Cl⁻ channel is somehow involved in the ischemic process. Actually, we previously reported injurious effects of CFTR Cl⁻ channel blockers and protective effects of CFTR Cl⁻ channel activators on cell viability in neonatal rat ventricular myocytes in primary culture after oxygen and glucose deprivation which mimics ischemia in vitro. Using a myocardial ischemia-reperfusion (I-R) system in vivo, we then investigated further the protective effect of CFTR activators on myocardial injury after 30-min occlusion of the left anterior descending coronary artery and 48-h reperfusion in male C57BL/6J mice. We injected a phosphodiesterase III inhibitor and PKC activator as CFTR Cl⁻ channel activators intravenously. Application of both agents, but not either alone, decreased markedly the infarct size compared to vehicle when these agents were given for 10 min before and during 30-min ischemia. Thus, it is concluded that the CFTR Cl⁻ channel activity exerts a protective action against ischemic injury in heart. [Jpn J Physiol 55 Suppl:S98 (2005)]