Referenced in: none

Automatically associated channels: Kir6.2

Title: Diadenosine tetraphosphate-gating of recombinant pancreatic ATP-sensitive K(+) channels.

Authors: S Jovanovic, A Jovanovic

Journal, date & volume: Biosci. Rep., 2001 Feb , 21, 93-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11508698

Abstract
Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic beta cells where targets ATP-sensitive K(+) (K(ATP)) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic K(ATP) channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic K(ATP) channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of K(ATP) channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes K(ATP) channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.