Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali

Pflugers Arch. 2001 Apr;442(1):64-72. doi: 10.1007/s004240000496.


TRAAK is a member of the tandem-pore K+ channel family, and is expressed mainly in the brain. Using rat TRAAK (rTRAAK), we studied its single-channel kinetics, interactive modes of activation, and the role of the C-terminus on its pressure-, fatty-acid- and pH-sensitivity. When expressed in COS-7 cells, rTRAAK showed a mildly inwardly rectifying single-channel current/voltage relationship in symmetrical 140 mM KCl. Unlike TREK-1 and TREK-2, which are activated by acidic conditions, rTRAAK was activated by alkali conditions, such that a change in intracellular pH from 7.3 to 8.3 and 8.8 increased channel activity 5- and 14-fold, respectively. Pressure and alkali produced a strong synergistic activation, and pressure and arachidonic acid (AA) produced a mild synergistic activation. The only additive effect was observed with alkali and AA. Replacing the C-terminus of rTRAAK with that of TASK-1 or TASK-3 did not affect the response to pressure, AA or alkali. In contrast, replacing the C-terminus of TREK-2 with that of TASK-3 abolished the sensitivity to AA and acid, but not to pressure. These results show that rTRAAK is an alkali-sensing K+ channel that shows synergistic activation with pressure, and that the mechanism of activation of rTRAAK and TREK by free fatty acids are different.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arachidonic Acid / pharmacology
  • Blotting, Northern
  • COS Cells
  • Cells, Cultured
  • Fatty Acids, Nonesterified / pharmacology*
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Kinetics
  • Molecular Sequence Data
  • Patch-Clamp Techniques
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Pressure*
  • Rats
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • Fatty Acids, Nonesterified
  • Kcnk4 protein, rat
  • Potassium Channels
  • Recombinant Proteins
  • Arachidonic Acid

Associated data

  • GENBANK/AF302842