Functional evidence linking potassium channels and afferent nerve-mediated mucosal protection in rat stomach

Adenosine triphosphate-dependent potassium (K+ATP) channels in several types of vascular smooth muscles mediate the vasodilation induced by calcitonin gene-related peptide (CGRP). Upon stimulation, primary afferent nerve terminals in the gastric mucosa release CGRP which mediates a protective hyperemia. We tested the hypothesis that a potassium channel blocker aggravates gastric mucosal injury by impairing afferent nerve-mediated hyperemia in the gastric mucosa. Rats were treated with K+ATP channel blocker, glybenclamide (20 mg/kg intravenously). Intragastric added ethanol (0.15 N HCl, 15% ethanol) and intragastric capsaicin (160 microM) were also administered. Glybenclamide aggravated the acidified ethanol-induced mucosal injury, and attenuated the mucosal hyperemia (hydrogen gas clearance) induced by intragastric acidified ethanol and intragastric capsaicin. These findings suggest for the first time that K+ATP channels modulate primary afferent nerve-mediated mucosal defense mechanisms in the gastric mucosa.