Referenced in: none

Automatically associated channels: Kv2.1

Title: Induction of a fast inactivation gating on delayed rectifier Shab K(+) channels by the anti-inflammatory drug celecoxib.

Authors: Imilla I Arias-Olguín, Elisa Carrillo, Bernardo Meza-Torres, Carolina Barriga-Montoya, Daniel Balleza, Froylan Gómez-Lagunas

Journal, date & volume: , 2011 Jan 18 , 5,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21084865

Abstract
Celecoxib is a drug designed to selectively inhibit COX-2, an inflammation-inducible cyclooxygenase isoform, over the constitutively expressed COX-1 isoform. In addition to this selective inhibition it is now known that celecoxib exerts a variety of effects on several types of ion channels, thus producing secondary physiological effects. In this work we demonstrate that at therapeutically relevant concentrations celecoxib interacts with Shab K(+) channels specifically promoting a fast inactivation gating (without blocking the pore or significantly affecting other gating processes). At least two celecoxib molecules bind to each channel promoting a fast inactivation that develops from both open and closed states. Channel inactivation in turn causes a reduction of the size of I(K). Taken together, our observations show that in addition to its intended therapeutic target celecoxib is a useful tool to further study the mechanism of Shab channel inactivation.