BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery.
Potassium (K+) channel openers decrease intracellular free Ca2+ concentrations ([Ca2+]i by hyperpolarizing the membrane and deactivating the Ca(2+)-channels. To examine whether the hyperpolarization produced by K(+)-channel openers has other effects on the mechanical activity of vascular smooth muscle, we investigated the effects of levcromakalim (BRL 38227) on membrane potential, [Ca2+]i, as measured with fura-2, and force of contraction induced by 30 mmol/l KCl-physiological salt solution (PSS), in canine coronary arteries. BRL 38227 hyperpolarized the membrane and reduced increases in [Ca2+]i and in contractile force induced by 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined in the presence of BRL 38227, was located to the right of the control curve determined by decreasing extracellular Ca2+ concentrations ([Ca2+]o) in 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined by decreasing extracellular K+ concentrations ([K+]o), was also located to the right of that determined by decreasing [Ca2+]o in 30 mmol/l KCl-PSS. The effect of BRL 38227, a reduction in the Ca(2+)-sensitivity of contractile elements, was antagonized by the ATP-sensitive K(+)-channel blocker, glibenclamide (10(-6) or 10(-5) mol/l). These results suggest that the membrane hyperpolarization induced by BRL 38227, or the repolarization caused by reducing [K+]o, decreases the Ca(2+)-sensitivity of contractile elements of vascular smooth muscle.
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Y
Y
Okada
T
T
Yanagisawa
N
N
Taira
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D011189:Potassium Chloride; D005905:Glyburide; D002118:Calcium