Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target?

J Med Chem. 2016 Jun 9;59(11):5149-57. doi: 10.1021/acs.jmedchem.5b00671. Epub 2015 Dec 14.


Potassium (K(+)) channels are membrane proteins expressed in most living cells that selectively control the flow of K(+) ions. More than 80 genes encode the K(+) channel subunits in the human genome. The TWIK-related K(+) channel (TREK-1) belongs to the two-pore domain K(+) channels (K2P) and displays various properties including sensitivity to physical (membrane stretch, acidosis, temperature) and chemical stimuli (signaling lipids, volatile anesthetics). The distribution of TREK-1 in the central nervous system, coupled with the physiological consequences of its opening and closing, leads to the emergence of this channel as an attractive therapeutic target. We review the TREK-1 channel, its structural and functional properties, and the pharmacological agents (agonists and antagonists) able to modulate its gating.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrhythmias, Cardiac / drug therapy
  • Depression / drug therapy
  • Epilepsy / drug therapy
  • Humans
  • Inflammation / drug therapy
  • Models, Molecular
  • Molecular Structure
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Pain / drug therapy
  • Potassium Channels, Tandem Pore Domain / agonists*
  • Potassium Channels, Tandem Pore Domain / antagonists & inhibitors*
  • Potassium Channels, Tandem Pore Domain / metabolism
  • Structure-Activity Relationship


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