Lysophosphatidic acid-operated K+ channels

J Biol Chem. 2005 Feb 11;280(6):4415-21. doi: 10.1074/jbc.M408246200. Epub 2004 Nov 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calcium / chemistry
  • Cations
  • Cell Survival
  • Cells, Cultured
  • Electrophysiology
  • Hydrogen-Ion Concentration
  • Ions
  • Kinetics
  • Ligands
  • Lipid Metabolism
  • Lysophospholipids / metabolism*
  • Mice
  • Models, Biological
  • Neurons / metabolism
  • PPAR gamma / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels / chemistry*
  • Potassium Channels / metabolism
  • Potassium Channels, Tandem Pore Domain / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction


  • Cations
  • Ions
  • Kcnk10 protein, mouse
  • Kcnk4 protein, mouse
  • Ligands
  • Lysophospholipids
  • PPAR gamma
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1
  • lysophosphatidic acid
  • Calcium