title: [Endothelin-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes through a p38 MAPK-independent signaling pathway].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, China. yuliangzhu73@163.com
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Yu
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
authors.forename: Tonghui
authors.initials: T
authors.lastname: She
authors.forename: Banghua
authors.initials: B
authors.lastname: Wang
authors.forename: Chunrong
authors.initials: C
authors.lastname: Shi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects*; D019332:Endothelin-1 / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D019332:Endothelin-1; D007093:Imidazoles; D009842:Oligopeptides; D010880:Piperidines; D011725:Pyridines; C086539:BQ 788; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580