SYNERGISTIC ACTION OF NS-004 AND INTERNAL CA2-ARTERY K+ CHANNELS( CONCENTRATION IN MODULATING PULMONARY)

Considering the singular vasomotor behavior of the pulmonary artery, w e were interested to test NS-004 rophenyl)-5-trifluoromethyl-2(3H)-ben zimidazolone) on pulmonary artery smooth muscle cells. Using the patch clamp technique, we identified a delayed rectifier K+ current and a C a2+-activated K+ current. With a low free intracellular Ca2+ concentra tion ([Ca2+](i)), 10-50 mu M NS-004 activated a noisy outward current which was blocked by iberiotoxin. 50 mu M NS-004 also inhibited a smoo th inactivating outward current. Under these conditions, 10 mu M NS-00 4 induced no change in the resting membrane potential. With a higher f ree [Ca2+](i), 10 mu M NS-004 was 3.5 times more efficacious in increa sing the noisy current and it induced a hyperpolarization, We conclude d that increasing free [Ca2+](i) induced potentiation of the NS-004-in duced activation of high conductance Ca2+-sensitive K+ channels and of the NS-004-induced hyperpolarization of the cell. The delayed rectifi er K+ channel was inhibited by NS-004 as well as by an increased free [Ca2+](i).