Effects of endothelin 1 on calcium and sodium currents in isolated human cardiac myocytes

Can J Physiol Pharmacol. 1995 Dec;73(12):1774-83. doi: 10.1139/y95-242.

Abstract

We have used the whole-cell voltage-clamp technique to study the effects of endothelin 1 (ET-1, 10 nM) on L-type Ca2+ currents and voltage-dependent Na+ inward currents in human cardiac cells. Myocytes were enzymatically isolated from atrial specimens obtained during open-heart surgery and from human ventricular tissues of explanted hearts. Extracellular application of ET-1 decreased the peak amplitude of Ca2+ currents by 26 +/- 6% (n = 13) in atrial myocytes and by 19 +/- 3% (n = 8) in ventricular myocytes. In three atrial cells, treatment with 1 microM BQ123 prevented the decrease in Ca2+ currents induced by ET-1. When GTP (0.2 mM) was added to the dialyzing pipette solution, ET-1 still caused a small decline by 12 +/- 5% (n = 16), in peak Ca2+ currents, in atrial myocytes. When Ca2+ currents were increased (+210 +/- 19%) by a beta-adrenoceptor agonist (0.1 microM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 microM), ET-1 reduced Ca2+ currents by 35 +/- 6% (n = 4) and 30 +/- 4% (n = 5), respectively. In human ventricular myocytes in the presence of 1 microM isoproterenol, which increased the peak Ca2+ currents by 150 +/- 30%, ET-1 also induced a drastic reduction in Ca2+ currents, by 40 +/- 11% (n = 5). The tetrodotoxin-sensitive Na+ currents measured in the presence of 5 mM [Na]o were significantly enhanced (+28 +/- 7%) by ET-1 in five atrial myocytes. The stimulatory effect of ET-1 on Na+ currents was partially reversible. The present findings in human cardiac cells show that ET-1 did not enhance the Ca2+ currents in the absence or presence of internal GTP. The positive inotropic actions induced by ET-1 in human heart may be mediated mainly by signal-transduction pathways other than the G-protein-adenylyl cyclase-cAMP system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Action Potentials / drug effects
  • Adult
  • Calcium Channels / drug effects*
  • Cell Separation
  • Drug Synergism
  • Endothelin-1 / pharmacology*
  • Female
  • Heart Atria / cytology
  • Heart Atria / drug effects
  • Heart Atria / metabolism
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Humans
  • Male
  • Middle Aged
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Sodium Channels / drug effects*

Substances

  • Calcium Channels
  • Endothelin-1
  • Receptors, Adrenergic, beta
  • Sodium Channels
  • 8-Bromo Cyclic Adenosine Monophosphate
  • 1-Methyl-3-isobutylxanthine