Lysophosphatidic acid-operated K+ channels.
Lysophosphatidic acid (LPA) is an abundant cellular lipid with a myriad of biological effects. It plays an important role in both inter- and intracellular signaling. Activation of the LPA1-3 G-protein-coupled receptors explains many of the extracellular effects of LPA, including cell growth, differentiation, survival, and motility. However, LPA also acts intracellularly, activating the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma that regulates gene transcription. This study shows that the novel subfamily of mechano-gated K2P channels comprising TREK-1, TREK-2, and TRAAK is strongly activated by intracellular LPA. The LPA-activated 2P domain K+ channels are intracellular ligand-gated K+ channels such as the Ca2+- or the ATP-sensitive K+ channels. LPA reversibly converts these mechano-gated, pH- and voltage-sensitive channels into leak conductances. Gating conversion of the 2P domain K+ channels by intracellular LPA represents a novel form of ion channel regulation. Thus, the TREK and TRAAK channels should be included in the LPA-associated physiological and disease states.
Chemin
Jean
J
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR 6097, Institut Paul Hamel, 660 route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
Patel
Amanda
A
Duprat
Fabrice
F
Zanzouri
Marc
M
Lazdunski
Michel
M
Honoré
Eric
E
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000737:chemistry; D002412:Cations; D002470:Cell Survival; D002478:Cells, Cultured; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D008024:Ligands; D050356:Lipid Metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D002412:Cations; D007477:Ions; C503445:Kcnk10 protein, mouse; C503433:Kcnk4 protein, mouse; D008024:Ligands; D008246:Lysophospholipids; D047495:PPAR gamma; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C032881:lysophosphatidic acid; D002118:Calcium