The Effect of Carbon Monoxide on Contraction, Cytosolic Ca<SUP>2&#8290;</SUP> Level and Ionic Currents in Guinea Pig Ileal Smooth Muscle

The Effect of Carbon Monoxide on Contraction, Cytosolic Ca<SUP>2&#8290;</SUP> Level and Ionic Currents in Guinea Pig Ileal Smooth Muscle

<P> The aim of this study was to clarify the mechanism of the inhibitory action of carbon monoxide (CO) on contraction, by measuring cytosolic Ca<SUP>2&#8290;</SUP> level ([Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>) 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 [Ca<SUP>2</SUP><SUP>&#8290;</SUP>]<SUB>i</SUB>. Cumulative addition of KCl induced a graded increase in [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> 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 [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> induced by cumulative addition of KCl was only slightly decreased in the presence of CO, and the [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>-tension relationship shifted downwards. Using the patch clamp technique with a holding potential of &#8291;60 mV, we found that CO had little effect on the peak Ba currents (I<SUB>Ba</SUB>) when voltage was stepped from &#8291;60 mV to 0 mV. In addition, CO showed no effect on the depolarization-activated outward K<SUP>&#8290;</SUP> currents in the all potential ranges. We conclude that CO inhibits smooth muscle contraction mainly by decreasing the Ca<SUP>2&#8290;</SUP> sensitivity of contractile elements via a cGMP-dependent pathway, not by involving L-type Ca<SUP>2&#8290;</SUP> and outward-potassium currents in guinea-pig ileum.