Carbon monoxide is an endogenous hyperpolarizing factor in the gastrointestinal tract.

In all mammalian species examined to date, there is a 10 mV or more gradient in resting membrane potential across the wall of the gastric antrum, small intestine and colon, and an even larger gradient along the long axis of the stomach. These voltage gradients, which may be considered biological rheostats, are central to the ability of circular smooth muscle to vary the strength of contraction from weak to propulsive and occluding. In this short review, we consider recent data that support the hypothesis that carbon monoxide generated in interstitial cells of Cajal is a hyperpolarizing factor for circular smooth muscle and the root of the essential voltage gradients.