Referenced in: none

Automatically associated channels: Kir6.2

Title: Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

Authors: Jocelyn E Manning Fox, Gunce Karaman, Michael B Wheeler

Journal, date & volume: Biochem. Biophys. Res. Commun., 2006 Nov 17 , 350, 492-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17011513

Abstract
Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.