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KMID : 0811720000040010033
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Korean Journal of Physiology & Pharmacology
2000 Volume.4 No. 1 p.33 ~ p.40
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The Effect of NO Donor on Contraction, Cytosolic Ca2 Level and Ionic Currents in Guinea-pig Ileal Smooth Muscle
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Seong-Chun Kwon/Seong-Chun Kwon
Ki-Young Park/Duck-Sun Ahn/Young-Ho Lee/Bok-Soon Kang
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Abstract
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This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on contraction, cytosolic Ca2+ level ([Ca2+]i) and ionic currents in guinea-pig ileum. SIN-1 (0.01∼100μM) inhibited 25 mM KCl- or histamine (10μM)?induced contraction in a concentration-dependent manner. SIN-1 reduced both the 25 mM KCl- and the histamine-stimulated increases in muscle tension in parallel with decreased [Ca2+]i. Using the patch clamp technique with a holding potential of -60 mV, SIN-1 (10μM) decreased peak Ba currents (IBa) by 30.9±5.4 (n=6) when voltage was stepped from -60 mV to +10 mV and this effect was blocked by ODQ (1μM), a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal IBa, and SIN-1 (10μM) inhibited peak IBa by 32.4±5.8 (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of -40 mV, application of 10μM histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by 10μM SIN-1, and this effect was abolished by ODQ (1μM). In addition, SIN-1 markedly increased the depolarization-activated outward K+ currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing [Ca2+]i resulted from the inhibition of L-type Ca2+ channels and the inhibition of nonselective cation currents and/or by the activation of K+ currents via a cGMP-dependent pathway.
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KEYWORD
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Intestinal smooth muscle relaxation, SIN-1, [Ca2 ]i, Ionic currents, Guinea-pig ileum,
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