BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery |
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Authors: | Yuji Okada Teruyuki Yanagisawa Norio Taira |
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Institution: | (1) Department of Pharmacology, Tohoku University School of Medicine, 980 Sendai, Japan |
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Abstract: | Summary Potassium (K+) channel openers decrease intracellular free Ca2+ concentrations (Ca2+]i) by hyperpolarizing the membrane and deactivating the Ca2+-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/1). These results suggest that the membrane hyperpolarization induced by BRL 38227, or the repolarization caused by reducing (K+]o), decreases the Ca2+-sensitivity of contractile elements of vascular smooth muscle.Correspondence to T. Yanagisawa at the above address |
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Keywords: | K+ channel opener Levcromakalim (BRL 38227) Hyperpolarization Repolarization Ca2+-sensitivity of contractile elements |
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