Referenced in: none

Automatically associated channels: HCN2 , HCN3 , HCN4

Title: [Endothelin-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes through a p38 MAPK-independent signaling pathway].

Authors: Liangzhu Yu, Mincai Li, Tonghui She, Banghua Wang, Chunrong Shi

Journal, date & volume: Nan Fang Yi Ke Da Xue Xue Bao, 2012 Sep , 32, 1274-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22985562

Abstract
To investigate the transcriptional regulation of pacemaker channel I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat ventricular myocytes and its mechanism.Neonatal rat ventricular myocytes were enzymatically isolated. I(f) current was recorded using the whole-cell patch-clamp technique. The expression of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by quantitative RT-PCR.ET-1 increased the expression of HCN2 and HCN4 mRNA in a dose- and time-dependent manner. These effects were blocked by specific ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-203580).These findings indicate that ET-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.