Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel

J Biol Chem. 1999 Sep 17;274(38):26691-6. doi: 10.1074/jbc.274.38.26691.


TREK-1 is a member of the novel structural class of K(+) channels with four transmembrane segments and two pore domains in tandem (1,2). TREK-1 is opened by membrane stretch and arachidonic acid. It is also an important target for volatile anesthetics (2,3). Here we show that internal acidification opens TREK-1. Indeed, lowering pH(i) shifts the pressure-activation relationship toward positive values and leads to channel opening at atmospheric pressure. The pH(i)-sensitive region in the carboxyl terminus of TREK-1 is the same that is critically involved in mechano-gating as well as arachidonic acid activation. A convergence, which is dependent on the carboxyl terminus, occurs between mechanical, fatty acids and acidic stimuli. Intracellular acidosis, which occurs during brain and heart ischemia, will induce TREK-1 opening with subsequent K(+) efflux and hyperpolarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / metabolism
  • Animals
  • COS Cells
  • Cells, Cultured
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Mice
  • Mutagenesis, Site-Directed
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Tandem Pore Domain*
  • Stress, Mechanical
  • Transfection


  • Acids
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1