CA2-ACTIVATED CL- CURRENTS ARE ACTIVATED BY METABOLIC INHIBITION IN RAT PULMONARY-ARTERY SMOOTH-MUSCLE CELLS()

We report the electrophysiological and functional properties of Ca2+-a ctivated Cl- currents [I-Cl(Ca)] in rat pulmonary artery smooth muscle and the activation of these currents by the metabolic inhibitor cyani de. Caffeine and norepinephrine (NE) evoked both Ca2+-activated K+ cur rents [I-K(Ca)] and I-Cl(Ca) currents in voltage-clamped myocytes (-50 mV). Niflumic acid (10 mu M) reduced the caffeine-induced I-Cl(Ca) by similar to 64% and reversibly reduced NE-induced tension. Exposure of myocytes to cyanide (2-10 mM) induced a slowly developing inward curr ent (-50 mV) in physiological and K+-free solutions, which was identif ied as I-Cl(Ca) on the basis of ion selectivity and Ca2+ dependence. C yanide elevated cytosolic Ca2+ concentration, and this elevation was m arkedly inhibited by preexposure to caffeine and slightly inhibited by nisoldipine. During exposure to caffeine, the Ca2+-activated K+ curre nt was also augmented. Cyanide markedly prolonged I-Cl(Ca) activated b y caffeine, increasing the half-decay time from 3.5 (control) to 29 s (cyanide); the half-decay time of the caffeine-induced I-K(Ca) was not significantly affected by cyanide. The results indicate that metaboli c inhibition increases [Ca2+](i) and activates a prolonged, depolarizi ng Cl- current in pulmonary artery myocytes.