The Effect of Carbon Monoxide on L-type Calcium Channel Currents in Human Intestinal Smooth Muscle Cells

The Effect of Carbon Monoxide on L-type Calcium Channel Currents in Human Intestinal Smooth Muscle Cells

Carbon monoxide (CO) is low molecular weight oxide gas that is endogenously produced under physiological conditions and interacts with another gas, nitric oxide (NO), to act as a gastrointestinal messenger. The aim of this study was to determine the effects of exogenous CO on L-type calcium channel currents of human jejunal circular smooth muscle cells. Cells were voltage clamped with 10 mM barium (Ba<SUP>2&#8290;</SUP>) as the charge carrier, and CO was directly applied into the bath to avoid perfusion induced effects on the recorded currents. 0.2% CO was increased barium current (I<SUB>Ba</SUB>) by 15&#8273;2% (mean&#8273;S.E., p<FONT FACE= 바탕 >＜0.01, n=11) in the cells. To determine if the effects of CO on barium current were mediated through the cGMP pathway, cells were pretreated with 1-H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10<FONT FACE= 바탕 >μM), a soluble guanylyl cyclase inhibitor, and exogenous CO (0.2%) had no effect on barium currents in the presence of ODQ (2&#8273;1% increase, n=6, p<FONT FACE= 바탕 >＞0.05). CO mediates inhibitory neurotransmission through the nitric oxide pathway. Therefore, to determine if the effects of CO on L-calcium channels were also mediated through NO, cells were incubated with N<SUP>G</SUP>-nitro-L-arginine (L-NNA, 1 mM), a nitric oxide synthase inhibitor. After L-NNA pretreatment, 0.2 % CO did not increase barium current (4&#8273;2% increase, n=6, p<FONT FACE= 바탕 >＞0.05). NO donor, SNAP (20<FONT FACE= 바탕 >μM) increased barium current by 13&#8273;2% (n=6, p<FONT FACE= 바탕 >＜0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.