Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2006 Nov 17;350(2):492-7. Epub 2006 Sep 26.

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

Author information

1
Department of Physiology, 3352 Medical Sciences Building, 1 King's College Circle, University of Toronto, Toronto, Ont., Canada. j.manningfox@utoronto.ca

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.

PMID:
17011513
DOI:
10.1016/j.bbrc.2006.09.084
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center