Endothelin-1 inhibits L-type Ca currents enhanced by isoproterenol in guinea-pig ventricular myocytes

Pflugers Arch. 1996 Feb;431(4):533-9. doi: 10.1007/BF02191900.


To investigate the action of endothelin-1 (ET-1) on L-type Ca currents (ICa,L) in guinea-pig ventricular cells, whole-cell currents were recorded at approximately 36-37 degrees C in enzymatically isolated myocytes. ET-1 (> or =10 nM) suppressed the basal ICa,L to 79+/-8% of control at 20 nM. Bath application of isoproterenol (ISO; 10 nM) enhanced ICa,L to 192+/-28% with about a -10-mV shift of its relationship with membrane potential. ET-1 concentration dependently inhibited this ISO-enhanced ICa,L with a half-maximally inhibitory concentration (IC50) of 168 pM. The inhibitory actions of ET-1 were antagonised by BQ-123 (300 nM), cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), a specific ETA receptor antagonist. Histamine-enhanced ICa,L was also suppressed by ET-1, but ICa, L potentiated by internal adenosine 3',5'-cyclic monophosphate (cAMP) was unaffected. Preincubation of myocytes with pertussis toxin (PTX, at 5 microgram/ml for >60 min at 36 degrees C) completely occluded the ET-1 action. Thus, stimulation of ETA receptors by subnanomolar ET-1 inhibits ICa,L via PTX-sensitive G-proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology
  • Colforsin / pharmacology
  • Cyclic AMP / pharmacology
  • Endothelins / pharmacology*
  • Guinea Pigs
  • Heart Ventricles / chemistry
  • Heart Ventricles / cytology
  • Histamine / pharmacology
  • Isoproterenol / pharmacology*
  • Membrane Potentials
  • Myocardium / chemistry
  • Myocardium / cytology*
  • Receptors, Endothelin / analysis


  • Calcium Channel Blockers
  • Calcium Channels
  • Endothelins
  • Receptors, Endothelin
  • Colforsin
  • Histamine
  • Cyclic AMP
  • Isoproterenol