MODULATION OF MEMBRANE CURRENTS AND MECHANICAL-ACTIVITY BY NIFLUMIC ACID IN RAT VASCULAR SMOOTH-MUSCLE

The effects of niflumic acid on whole-cell membrane currents and mecha nical activity were examined in the rat portal vein. In freshly disper sed portal vein cells clamped at -60 mV in caesium (Cs+)-containing so lutions, niflumic acid (1-100 mu M) inhibited calcium (Ca2+)-activated chloride currents (I-Cl(Ca)) induced by caffeine (10 mM) and by norad renaline (10 mu M). In a potassium (K+)-containing solution and at a h olding potential of -10 mV, niflumic acid (10-100 mu M) induced an out ward K+ current (l(K(ATP))) which was sensitive to glibenclamide (10-3 0 mu M). At concentrations < 30 mu M and at a holding potential of -2 mV, niflumic acid had no effect on the magnitude of the caffeine- or n oradrenaline-stimulated current (l(BK(Ca))) carried by the large condu ctance, Ca2+-sensitive K+ channel (BKCa). However, at a concentration of 100 mu M, niflumic acid significantly inhibited I-BK(Ca) evoked by caffeine (10 mM) but not by NS1619 hylphenyl)-5-trifluoromethyl-2(3H)b enzimidazolone; 20 mu M). In Cs+-containing solutions, niflumic acid ( 10-100 mu M) did not inhibit voltage-sensitive Ca2+ currents. In intac t pol tal veins, niflumic acid (1-300 mu M) inhibited spontaneous mech anical activity, an action which was partially antagonised by glibencl amide (1-10 mu M), and contractions produced by noradrenaline (10 mu M ), an effect which was glibenclamide-insensitive. It is concluded that inhibition of I-Cl(Ca), and stimulation of I-K(ATP) both contribute t o the mechano-inhibitory actions of niflumic acid in the rat portal ve in.