title: Oscillatory Cl- current induced by angiotensin II in rat pulmonary arterial myocytes: Ca2+ dependence and physiological implication.
abstract: We have previously reported that angiotensin II (ANG II) induces oscillations in the cytoplasmic calcium concentration ([Ca2+]i) of pulmonary vascular myocytes. The present work was undertaken to investigate the effect of ANG II in comparison with ATP and caffeine on membrane currents and to explore the relation between these membrane currents and [Ca2+]i. In cells clamped at -60 mV, ANG II (10 microM) or ATP (100 microM) induced an oscillatory inward current. Caffeine (5 mM) induced only one transient inward current. In control conditions, the reversal potential (Erev) of these currents was close to the equilibrium potential for Cl- ions (Ecl = -2.1 mV) and was shifted towards more positive values in low-Cl- solutions. Niflumic acid (10-50 microM) and DIDS (0.25-1 mM) inhibited this inward current. Combined recordings of membrane current and [Ca2+]i by indo-1 microspectrofluorimetry revealed that ANG II- and ATP-induced currents occurred simultaneously with oscillations in [Ca2+]i whereas the caffeine-induced current was accompanied by only one transient increase in [Ca2+]i. Niflumic acid (25 microM) had no effect on agonist-induced [Ca2+]i responses, whereas thapsigargin (1 microM) abolished both membrane current and the [Ca2+]i response. Heparin (5 mg/ml in the pipette solution) inhibited both [Ca2+]i responses and membrane currents induced by ANG II and ATP, but not by caffeine. In pulmonary arterial strips, ANG II-induced contraction was inhibited by niflumic acid (25 microM) or nifedipine (1 microM) to the same extent and the two substances did not have an additive effect. This study demonstrates that, in pulmonary vascular smooth muscle, ANG II, as well as ATP, activate an oscillatory calcium dependent chloride current which is triggered by cyclic increases in [Ca2+]i and that both oscillatory phenomena are primarily IP3-mediated. It is suggested that ANG II-induced oscillatory chloride current could depolarise the cell membrane leading to activation of voltage-operated Ca2+ channels. The resulting Ca2+ influx contributes to the component of ANG II-induced contraction that is equally sensitive to chloride or calcium channel blockade.
authors.affiliation: Laboratoire de Physiologie Cellulaire Respiratoire, Université Bordeaux 2, France.
authors.forename: C
authors.initials: C
authors.lastname: Guibert
authors.forename: R
authors.initials: R
authors.lastname: Marthan
authors.forename: J P
authors.initials: JP
authors.lastname: Savineau
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007211:Indoles; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D000804:Angiotensin II; D002110:Caffeine; D009544:Niflumic Acid; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D009543:Nifedipine; C048960:indo-1; D002118:Calcium