ACTIVATION OF WHOLE-CELL CURRENTS IN ISOLATED HUMAN JEJUNAL CIRCULAR SMOOTH-MUSCLE CELLS BY CARBON-MONOXIDE

Carbon monoxide (CO) is a low molecular weight oxide produced endogeno usly from fatty acids and heme protein. A physiological role for CO ha s been suggested for vascular smooth muscle, hemostasis, and olfactory neurons, but direct evidence is lacking. Heme oxygenase, which cataly zes the formation of CO from heme proteins, is present in small intest inal smooth muscle. The effect of 1% CO on whole cell currents in norm al human jejunal circular muscle cells was studied with the use of a p erforated patch-clamp technique. A 1% CO-containing Krebs solution cau sed an initial and transient increase in whole cell current in 20 of 2 2 cells tested (175 +/- 40%, mean +/- SE) and a transient hyperpolariz ation (15.6 +/- 3.6 mV, mean +/- SE) of the membrane potential. During prolonged recordings, 1% CO evoked ongoing cyclic increases and decre ases in the whole cell current. Each current increase was accompanied by a sharp membrane hyperpolarization. These data suggest that CO may modulate whole cell potassium current and membrane potential.