Simultaneous Activation of p38 MAPK and p42/44 MAPK by ATP Stimulates the K+ Current ITREK in Cardiomyocytes

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-cl...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-12, Vol.275 (50), p.39110-39116
Main Authors: Aimond, Franck, Rauzier, Jean-Michel, Bony, Claire, Vassort, Guy
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acid - pharmacology
Blotting, Western
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cells, Cultured
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Cytosol - enzymology
Embryo, Mammalian - metabolism
Enzyme Activation
Enzyme Inhibitors - pharmacology
Heart Ventricles - metabolism
Ions
Mice
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - metabolism
Models, Biological
Myocardium - metabolism
p38 Mitogen-Activated Protein Kinases
Patch-Clamp Techniques
Phospholipases A - antagonists & inhibitors
Phospholipases A - metabolism
Potassium - metabolism
Potassium Channels - metabolism
Potassium Channels, Tandem Pore Domain
Protein-Tyrosine Kinases - metabolism
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases, 90-kDa
RNA, Messenger - metabolism
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Summary: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 ITREKimplies 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M008192200