Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype

Nat Neurosci. 2006 Sep;9(9):1134-41. doi: 10.1038/nn1749. Epub 2006 Aug 13.


Depression is a devastating illness with a lifetime prevalence of up to 20%. The neurotransmitter serotonin or 5-hydroxytryptamine (5-HT) is involved in the pathophysiology of depression and in the effects of antidepressant treatments. However, molecular alterations that underlie the pathology or treatment of depression are still poorly understood. The TREK-1 protein is a background K+ channel regulated by various neurotransmitters including 5-HT. In mice, the deletion of its gene (Kcnk2, also called TREK-1) led to animals with an increased efficacy of 5-HT neurotransmission and a resistance to depression in five different models and a substantially reduced elevation of corticosterone levels under stress. TREK-1-deficient (Kcnk2-/-) mice showed behavior similar to that of naive animals treated with classical antidepressants such as fluoxetine. Our results indicate that alterations in the functioning, regulation or both of the TREK-1 channel may alter mood, and that this particular K+ channel may be a potential target for new antidepressants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antidepressive Agents / pharmacology
  • Behavior, Animal / drug effects
  • Depressive Disorder / genetics
  • Depressive Disorder / physiopathology*
  • Depressive Disorder / prevention & control
  • Drug Resistance / genetics
  • Fluoxetine / pharmacology
  • Gene Deletion*
  • Genotype
  • Mice
  • Mice, Knockout
  • Phenotype
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / physiology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Serotonin / metabolism
  • Synaptic Transmission / drug effects


  • Antidepressive Agents
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1
  • Fluoxetine
  • Serotonin