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Originally published In Press as doi:10.1074/jbc.M008192200 on September 18, 2000

J. Biol. Chem., Vol. 275, Issue 50, 39110-39116, December 15, 2000
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Simultaneous Activation of p38 MAPK and p42/44 MAPK by ATP Stimulates the K+ Current ITREK in Cardiomyocytes*

Franck AimondDagger , Jean-Michel Rauzier, Claire Bony, and Guy Vassort§

From INSERM U-390, Physiopathologie cardiovasculaire, IFR N° 3, CHU Arnaud de Villeneuve, F-34295 Montpellier Cedex 5, France

Living cells exhibit multiple K+ channel proteins; among these is the recently reported atypical two-pore domain K+ channel protein TREK-1. Most K+ currents are modulated by neurohormones and under various pathological conditions. Here, in rat ventricular cardiomyocytes using the whole-cell patch-clamp technique, we characterize for the first time a native TREK-1-like current (ITREK) that is activated by ATP, a purine agonist applied at a micromolar range. This current is sensitive to arachidonic acid, intracellular acidosis, and various K+ current inhibitors. Reverse transcription-polymerase chain reaction reveals the presence of a TREK-1-like mRNA in rat cardiomyocytes that shows 93% identity with mouse TREK-1. ATP effects are greatly attenuated in the presence of arachidonic acid or HCO-3-induced intracellular acidosis. Using a series of inhibitors, we further demonstrate that the ATP-induced stimulation of ITREK implies the activation of cytosolic phospholipase A2 and the release of arachidonic acid. These events require the simultaneous involvement of p38 MAPK and p42/44 MAPK, respectively, via a cAMP-dependent protein kinase and a tyrosine kinase pathway, whereas the two MAPKs conjugate to activate a mitogen- and stress-activated protein kinase (MSK-1). Our results thus demonstrate the occurrence of a TREK-1-like current in cardiac cells whose activation by purine agonists implies a dual-MAPK cytosolic pathway.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger A recipient of a grant from the Fondation pour la Recherche Médicale.

§ To whom correspondence should be addressed. Tel.: 33-4-67-41-52-41; Fax: 33-4-67-41-52-42; E-mail: vassort@montp.inserm.fr.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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