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KMID : 0811720000040060479
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Korean Journal of Physiology & Pharmacology
2000 Volume.4 No. 6 p.479 ~ p.486
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The Effect of Carbon Monoxide on Contraction, Cytosolic Ca2+ Level and Ionic Currents in Guinea Pig Ileal Smooth Muscle
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Taick Sang Nam/Seong Chun Kwon
Seung Soo Chung/Yun Suk Kim/Taick Sang Nam
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Abstract
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The aim of this study was to clarify the mechanism of the inhibitory action of carbon monoxide (CO) on contraction, by measuring cytosolic Ca2+ level ([Ca2+]i) and ionic currents in guinea-pig ileum. CO (10%) inhibited 40 mM KCl-induced contraction and this effect was blocked by ODQ (1μM), a soluble guanylyl cyclase (sGC) inhibitor. CO inhibited the 40 mM KCl-induced contraction without changing [Ca2+]i. Cumulative addition of KCl induced a graded increase in [Ca2+]i and muscle tension. In the presence of CO, cumulative addition of KCl induced smaller contraction than in the absence of CO. On the other hand, the increase in [Ca2+]i induced by cumulative addition of KCl was only slightly decreased in the presence of CO, and the [Ca2+]i?tension relationship shifted downwards. Using the patch clamp technique with a holding potential of -60 mV, we found that CO had little effect on the peak Ba currents (IBa) when voltage was stepped from -60 mV to 0 mV. In addition, CO showed no effect on the depolarization-activated outward K+ currents in the all potential ranges. We conclude that CO inhibits smooth muscle contraction mainly by decreasing the Ca2+ sensitivity of contractile elements via a cGMP-dependent pathway, not by involving L-type Ca2+ and outward-potassium currents in guinea-pig ileum.
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KEYWORD
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Carbon monoxide, Intestinal smooth muscle relaxation, cGMP,
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