Endothelin-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes through a p38 MAPK-independent signaling pathway.
- Author:
Liangzhu YU
1
;
Mincai LI
;
Tonghui SHE
;
Banghua WANG
;
Chunrong SHI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Cyclic Nucleotide-Gated Cation Channels; drug effects; Endothelin-1; metabolism; Imidazoles; pharmacology; Myocytes, Cardiac; drug effects; metabolism; Oligopeptides; pharmacology; Patch-Clamp Techniques; Piperidines; pharmacology; Pyridines; pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects; p38 Mitogen-Activated Protein Kinases; metabolism
- From: Journal of Southern Medical University 2012;32(9):1274-1279
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSNeonatal 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.
RESULTSET-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).
CONCLUSIONThese 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.
