title: Endothelin depolarizes myocytes from porcine coronary and human mesenteric arteries through a Ca-activated chloride current.
abstract: The effect of endothelin (ET) on membrane potential and current was studied in myocytes isolated from porcine coronary or from human mesenteric arteries at 3.6 mM extracellular Ca2+ concentration and 37 degrees C. ET (1-100 nM) induced cell shortening and membrane depolarization from a resting potential of -50 mV to about -15 mV. Ca currents (ICa, L-type) were transiently reduced by ET. At -50 mV, ET induced an inward current that peaked within 2 s and fell within 10 s to a sustained level. The current could be enlarged by reducing bath extracellular Cl- ion concentration, but removal of extracellular Na+ ions had no effect. The voltage dependence suggests that the ET-induced current is a Cl current (ICl) at potentials negative to -30 mV; at more positive potentials K currents (IK,Ca) are superimposed. The effects of ET on ICa, ICl, IK,Ca and contraction were prevented by intracellular Ca chelators, suggesting a Ca-dependent activation mechanism. The ET effects were abolished by pretreatment with 20 mM caffeine or prior cell-dialysis with heparin [thought to block inositol triphosphate-induced sarcoplasmic reticular Ca release]. The results suggest that ET releases Ca from the SR through a phosphoinositol response and that the released Ca acts as second messenger in modulating the membrane currents.
authors.affiliation: Department of Physiology, University of Cologne, Federal Republic of Germany.
authors.forename: U
authors.initials: U
authors.lastname: Klöckner
authors.forename: G
authors.initials: G
authors.lastname: Isenberg
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D016232:Endothelins; D007473:Ion Channels; D008565:Membrane Proteins; D002110:Caffeine; D002118:Calcium