Synergistic action of NS-004 and internal Ca2+ concentration in modulating pulmonary artery K+ channels.
Considering the singular vasomotor behavior of the pulmonary artery, we were interested to test NS-004 (1-(2'-hydroxy-5'-chlorophenyl)-5-trifluoromethyl-2(3H)-benzimidazolo ne) on pulmonary artery smooth muscle cells. Using the patch clamp technique, we identified a delayed rectifier K+ current and a Ca(2+)-activated K+ current. With a low free intracellular Ca2+ concentration ([Ca2+]i), 10-50 microM NS-004 activated a noisy outward current which was blocked by iberiotoxin. 50 microM NS-004 also inhibited a smooth inactivating outward current. Under these conditions, 10 microM NS-004 induced no change in the resting membrane potential. With a higher free [Ca2+]i, 10 microM NS-004 was 3.5 times more efficacious in increasing the noisy current and it induced a hyperpolarization. We concluded that increasing free [Ca2+]i induced potentiation of the NS-004-induced activation of high conductance Ca(2+)-sensitive K+ channels and of the NS-004-induced hyperpolarization of the cell. The delayed rectifier K+ channel was inhibited by NS-004 as well as by an increased free [Ca2+]i.
Vandier
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C
Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, CNRS EP-21, Tours, France.
Bonnet
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P
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002733:Chlorophenols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015221:Potassium Channels / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001562:Benzimidazoles; D002733:Chlorophenols; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C083230:NS 004; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D002118:Calcium