Effect of Kv7 channel modulators on the contractility of diabetic rat stomach in-vitro

Abstract

Objectives:To study the effect of KV7 channel modulators, Retigabine(KV7 opener) and XE-99 (KV7 blocker), on motility of both fundal and corpal gastric segments in Type I diabetic rats . Method:24 Male Sprague Dawley rats were divided into 2 groups: (I) control& (II) diabetic group (n=12) each were subdivided into 2 subgroups according to the used segment whether fundus or corpus. Each segment group was treated with retigabine and XE-991 on basal and cholinergic stimulated motility. The motility was recorded in-vitro using the Power Lab system. Results: Diabetic stomach significantly showed higher fundal basal amplitude and frequency of contractions when compared with control. Diabetic gastric response to A.ch. was significantly higher as compaired to control. Retigabine, significantly decreased spontaneous contractility of gastric fundal and corpal muscle in diabetic and control rats but diabetic group exhibits significant more decrease in contractility than control. Also, retigabine significantly decreased contractility of cholinergic stimulated fundal and corpal strips with significant more decreased contraction amplitude in diabetic corpus than the control. XE-991, significantly increased spontaneous gastric fundal and corpal contractility in diabetic and control rats but diabetic group exhibits significant more increased contraction in response to XE-991 than the control. Also, XE-991 after A.ch significantly increased the amplitude of fundal and corpal contractility of both diabetic and control groups with significant higher contraction in diabetics , however there is no increase in the tone after A.ch in either groups. Conclusion: KV7 channel modulators could affect gastric activity in type I diabetic and control rats.