The Effect of Carbon Monoxide on Contraction, Cytosolic $Ca^{2+}$ Level and Ionic Currents in Guinea Pig Ileal Smooth Muscle

The aim of this study was to clarify the mechanism of the inhibitory action of carbon monoxide (CO) on contraction, by measuring cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. CO (10%) inhibited 40 mM KCl-induced contraction and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase (sGC) inhibitor. CO inhibited the 40 mM KCl-induced contraction without changing $[Ca^{2+}]_i.$ Cumulative addition of KCl induced a graded increase in $[Ca^{2+}]_i$ 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 $[Ca^{2+}]_i$ induced by cumulative addition of KCl was only slightly decreased in the presence of CO, and the $[Ca^{2+}]_i-tension$ 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 $(I_{Ba})$ 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 $Ca^{2+}$ sensitivity of contractile elements via a cGMP-dependent pathway, not by involving L-type $Ca^{2+}$ and outward-potassium currents in guinea-pig ileum.