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