Endothelin-1 inhibits pacemaker currents in rabbit SA node cells

J Cardiovasc Pharmacol. 1998:31 Suppl 1:S440-2. doi: 10.1097/00005344-199800001-00126.

Abstract

Our recent study demonstrated that endothelin-1 (ET-1) inhibits the pacemaker activity of sinoatrial (SA) node cells via changes in the L-type Ca2+, delayed K+, and background K+ currents. Using the whole-cell patch-clamp technique in the same preparation, we found that ET-1 reduces other pacemaker currents, the T-type Ca2+ current (ICa,T) and the hyperpolarization-activated inward current (I(f)). The inhibitory actions of ET-1 on these currents were concentration-dependent, i.e., EC50 of 0.9 nM for ICa,T and 2.3 nM for I(f), with little reversal after washout of the peptide. In the presence of BQ485, both currents were not affected by ET-1. These results indicate additional mechanisms underlying negative chronotropic actions of ET-1 on the rabbit SA node.

MeSH terms

  • Animals
  • Azepines / pharmacology
  • Biological Clocks / drug effects*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Endothelin-1 / pharmacology*
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Oligopeptides / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Rabbits
  • Sinoatrial Node / cytology
  • Sinoatrial Node / drug effects*
  • Sinoatrial Node / physiology*

Substances

  • Azepines
  • Calcium Channels
  • Endothelin-1
  • Oligopeptides
  • Potassium Channels
  • BQ 485