Korean J Physiol Pharmacol.  2003 Dec;7(6):357-362.

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

• Lim I

Abstract

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 (Ba2+) 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 (Ba) ) by 15+/-2% (mean+/-S.E., p< 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 microM), a soluble guanylyl cyclase inhibitor, and exogenous CO (0.2%) had no effect on barium currents in the presence of ODQ (2+/-1% increase, n=6, p> 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 (G) -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+/-2% increase, n=6, p> 0.05). NO donor, SNAP (20 microM) increased barium current by 13+/-2% (n=6, p< 0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.

Keyword

L-type calcium channels; Carbon monoxide (CO); Human intestinal smooth muscle cells

MeSH Terms

Barium
Baths
Calcium Channels, L-Type*
Carbon Monoxide*
Carbon*
Guanylate Cyclase
Humans*
Molecular Weight
Muscle, Smooth*
Myocytes, Smooth Muscle*
Nitric Oxide
Nitric Oxide Synthase
Perfusion
Synaptic Transmission
Tissue Donors
Barium
Calcium Channels, L-Type
Carbon
Carbon Monoxide
Guanylate Cyclase
Nitric Oxide
Nitric Oxide Synthase