Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels

Neuron. 2014 Dec 17;84(6):1198-212. doi: 10.1016/j.neuron.2014.11.017. Epub 2014 Dec 11.


Mechanical and thermal activation of ion channels is central to touch, thermosensation, and pain. The TRAAK/TREK K(2P) potassium channel subfamily produces background currents that alter neuronal excitability in response to pressure, temperature, signaling lipids, and anesthetics. How such diverse stimuli control channel function is unclear. Here we report structures of K(2P)4.1 (TRAAK) bearing C-type gate-activating mutations that reveal a tilting and straightening of the M4 inner transmembrane helix and a buckling of the M2 transmembrane helix. These conformational changes move M4 in a direction opposite to that in classical potassium channel activation mechanisms and open a passage lateral to the pore that faces the lipid bilayer inner leaflet. Together, our findings uncover a unique aspect of K(2P) modulation, indicate a means for how the K(2P) C-terminal cytoplasmic domain affects the C-type gate which lies ∼40Å away, and suggest how lipids and bilayer inner leaflet deformations may gate the channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Ion Channel Gating / physiology*
  • Lipid Bilayers / metabolism
  • Mutation
  • Oocytes
  • Physical Stimulation
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Protein Structure, Secondary
  • Temperature*
  • Xenopus laevis


  • KCNK4 protein, human
  • Lipid Bilayers
  • Potassium Channels