KATP channel agonists preserve connexin43 protein in infarcted rats by a protein kinase C‐dependent pathway

作者：Tsung‐Ming Lee, Chih‐Chan Lin, Hsiao‐Yin Lien, Chien‐Chang Chen · 发表于：Journal of Cellular and Molecular Medicine · 年份：2011 · DOI：10.1111/j.1582-4934.2011.01366.x · 被引用次数：9 · 研究领域：Connexins and lens biology、Cardiac Ischemia and Reperfusion、Cardiac electrophysiology and arrhythmias

Downward remodelling of gap junctional proteins between myocytes may trigger ventricular arrhythmia after myocardial infarction. We have demonstrated that ATP-sensitive potassium (K(ATP)) channel agonists attenuated post-infarction arrhythmias. However, the involved mechanisms remain unclear. The purpose of this study was to determine whether K(ATP) channel agonists can attenuate arrhythmias through preserving protein kinase C (PKC)-(ε)dependent connexin43 level after myocardial infarction. Male Wistar rats after ligating coronary artery were randomized to either vehicle, nicorandil, pinacidil, glibenclamide or a combination of nicorandil and glibenclamide or pinacidil and glibenclamide for 4 weeks. To elucidate the role of PKC(ε) in the modulation of connexin43 level, carbachol and myristoylated PKC(ε) V1-2 peptide were also assessed. Myocardial connexin43 level was significantly decreased in vehicle-treated infarcted rats compared with sham. Attenuated connexin43 level was blunted after administering K(ATP) channel agonists, assessed by immunofluorescent analysis, Western blotting, and real-time quantitative reverse transcription-PCR of connexin43. Arrhythmic scores during programmed stimulation in the K(ATP) channel agonists-treated rats were significantly lower than those treated with vehicle. The beneficial effects of K(ATP) channel agonists were blocked by either glibenclamide or 5-hydroxydecanoate. Addition of the PKC activator, phorbol 12-myristate 13-acetate and the ...