Ca(2+)-activated Cl- currents are activated by metabolic inhibition in rat pulmonary artery smooth muscle cells.
We report the electrophysiological and functional properties of Ca(2+)-activated Cl- currents [ICl(Ca)] in rat pulmonary artery smooth muscle and the activation of these currents by the metabolic inhibitor cyanide. Caffeine and norepinephrine (NE) evoked both Ca(2+)-activated K+ currents [IK(Ca)] and ICl(Ca) currents in voltage-clamped myocytes (-50 mV). Niflumic acid (10 microM) reduced the caffeine-induced ICl(Ca) by approximately 64% and reversibly reduced NE-induced tension. Exposure of myocytes to cyanide (2-10 mM) induced a slowly developing inward current (-50 mV) in physiological and K(+)-free solutions, which was identified as ICl(Ca) on the basis of ion selectivity and Ca2+ dependence. Cyanide elevated cytosolic Ca2+ concentration, and this elevation was markedly inhibited by preexposure to caffeine and slightly inhibited by nisoldipine. During exposure to caffeine, the Ca(2+)-activated K+ current was also augmented. Cyanide markedly prolonged ICl(Ca) activated by caffeine, increasing the half-decay time from 3.5 (control) to 29 s (cyanide); the half-decay time of the caffeine-induced IK(Ca) was not significantly affected by cyanide. The results indicate that metabolic inhibition increases [Ca2+]i and activates a prolonged, depolarizing Cl- current in pulmonary artery myocytes.
Wang
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Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA.
Wang
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Yu
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Kotlikoff
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D003486:Cyanides / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004553:Electric Conductivity; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002712:Chlorides; D003486:Cyanides; D014662:Vasoconstrictor Agents; D002110:Caffeine; D009544:Niflumic Acid; D002118:Calcium; D009638:Norepinephrine