CB1 and TRPV1 receptors mediate protective effects on colonic electrophysiological properties in mice

Abstract

CB1 and TRPV1 receptors modulate enteric neurotransmission and colonic inflammation. This study investigates early electrophysiological changes in distal colon of wild-type and receptor deficient mice after an inflammatory insult set by dinitrobenzene sulfonic acid (DNBS). Colitis was induced by DNBS in CB1(-/-) mice, TRPV1(-/-) mice, and their respective wild-type littermates. Electrophysiological properties consisting of membrane potentials and electrically induced inhibitory junction potentials (IJP) of circular smooth muscle cells were evaluated at different time points. Additionally a histological colitis severity score was evaluated in CB1(+/+) and CB1(-/-) mice 24 h after DNBS. Inflammation caused spontaneous atropine insensitive rhythmic action potentials in CB1(-/-) and TRPV1(-/-) mice but not in wild-type animals. This indicates that membrane stability is disturbed, which in turn indicates a lack of protective mechanisms. Focal electrical neuronal stimulation of the myenteric plexus induced IJP in the smooth muscle cells. Twenty-four hours after initiation of inflammation, the duration of the IJP is prolonged in all animals, indicating disturbances within neuromuscular interaction. In CB1(-/-) mice, it is interesting that the duration of IJP was significantly extended, as compared to CB1(+/+) mice pointing toward missing protective mechanisms in the CB1(-/-) mice. Inflammatory insults in the mouse colon induce reproducible changes in the electrophysiological properties and such changes correlate with duration of colitis. In mutants, these electrophysiological changes display different patterns, suggesting the lack of protective properties for neuromuscular interactions and membrane stability.