Referenced in: none

Automatically associated channels: HCN2 , HCN3 , HCN4

Title: Spironolactone diminishes spontaneous ventricular premature beats by reducing HCN4 protein expression in rats with myocardial infarction.

Authors: Tao Song, Jing Yang, Yuan Yao, Haitao Li, Yongjun Chen, Jun Zhang, Congxin Huang

Journal, date & volume: Mol Med Report, 2011 May-Jun , 4, 569-73

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21468609

Abstract
Hyperpolarization-activated current (If) is the major ionic current contributing to the spontaneous diastolic depolarization of cardiac sinus node pacemaker cells. It is mediated by hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. However, several observations support a potential role of HCN channels in the arrhythmogenesis of working myocardium under pathological conditions. Spironolactone, a classic aldosterone blocker, has been proved to prevent spontaneous ventricular arrhythmias after myocardial infarction (MI). Here, we examined the effect of spironolactone on the expression of HCN channels and ventricular premature beats (VPBs) using a rat MI model. Sprague-Dawley rats were divided into a sham-operated group and MI groups treated with intragastric administration of saline or spironolactone (80 µg/kg/day) for 7 days immediately after ligation of the left coronary artery. Compared to the sham group, HCN2 and HCN4 protein levels were increased in MI rats. Treatment with spironolactone prevented the MI-induced increase of HCN4 protein levels (1.47 ± 0.16 vs. 1.81 ± 0.21, P<0.05). MI rats exhibited a marked increase of VPBs compared to the sham group (104 ± 17 vs. 3 ± 1 VPBs/h, P < 0.05). This the increase was reduced by spironolactone (55 ± 14 vs. 104 ± 17 VPBs/h, P < 0.05). Moreover, If current inhibitor (ivabradine, 0.5 mg/kg) further decreased the occurrence of VPBs in the control and spironolactone groups to the same level (54 ± 13 vs. 49 ± 8 VPBs/h, P > 0.05). In conclusion, spironolactone may prevent ischemia-induced VPBs by reducing HCN4 protein expression to basal levels.