Motor dysfunction of gastric antral smooth muscle in diabetic rats: Contribution of ATP-dependent potassium channels

Abstract

Background: The goal of the current research was to further elucidate the role of adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels in the motility and contractility force of gastric smooth muscle of diabetic rats. Materials and Methods: Male Wistar rats (190-230 g) were grouped into control and streptozotocin (STZ)-induced diabetes (55 mg/kg) rats. Thirty days later, gastric muscle contractility was measured using a myograph and a force transducer of antral segments immersed in a tissue bath. Gastric emptying response was measured through feeding of standard pellet. Furthermore, the expression of K-ATP channel subunits in antral smooth muscle was determined by western blot technique. Results: The amplitude of KCl-evoked twitch contractions of diabetic antral strips was about 25 more than control (P < 0.05). Application of minoxidil, a K-ATP channel opener, dose dependently decreased the force of twitch contractions in both normal and diabetic antral strips. Application of 10 mu M glibenclamide, a K-ATP channel blocker, did not antagonize the minoxidil-induced relaxation of antral strips. Diabetic gastric emptying was faster than normal, although not significant. Despite the relaxant effect of minoxidil on gastric emptying rate in normal rats (P < 0.05), this effect was not observed in diabetic rats. Also, glibenclamide increased gastric emptying and antagonized minoxidil-induced relaxation in normal rats (P < 0.05). Furthermore, the expression of K-ATP Kir6.1 and SUR2B subunits was substantially reduced in antral smooth muscle in diabetic condition (P < 0.01). Conclusion: These results propose that K-ATP channels may contribute to the development of gastric motility disorders in diabetes.