Regulation of AT1-calcineurin Signaling Pathway on Transient Outward Potassium Ion Channel Remolding in Hypertrophic Atrial Myocytes of Neonatal Rats / 中国循环杂志

ABSTRACT

Objective: To explore the role of angiotensin receptor type I (AT1)-calcineurin (CaN) signaling pathway in transient outward potassium ion channel (Ito) remolding in hypertrophic atrial myocytes of neonatal rats. Methods: 1 day old neonatal rats’ atrial myocytes were isolated and the cells were divided into 4 groups①Control group, normal cells were cultured for 24 h,②Stretching group, the cells were cultured for 24 h with mechanical stretching to induce hypertrophy,③Telmisartan group, the cells were treated by telmisartan at 1 μmol/L for 1 h, then cultured for 24 h and ④Cyclosporin-A (CsA) group, the cells were treated by CsA at 0.25 μg/ml for 1 h, then cultured for 24 h. The ratios of protein/DNA in myocytes were compared between Control group and Stretching group, cell hypertrophy was deifned by mRNA expression of atrial natriuretic peptide (ANP). Ito changes were detected by whole-cell patch clamping technique, proteins expressions of Kv4.3 and CaN A subunit were examined by Western blot analysis. Results: Compared with Control group, Stretching group showed obviously decreased Ito density and Kv4.3 protein expression, while increased CaN A protein expression; Compared with Stretching group, the above effects were reduced in Telmisartan group and CsA group. Conclusion: AT1-CaN signaling pathway was involved in the regulation of Ito channel remodeling in hypertrophic atrial myocytes of neonatal rats.