Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype.
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.
Heurteaux
Catherine
C
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université de Nice Sophia Antipolis, Institut Paul Hamel, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
Lucas
Guillaume
G
Guy
Nicolas
N
El Yacoubi
Malika
M
Thümmler
Susanne
S
Peng
Xiao-Dong
XD
Noble
Florence
F
Blondeau
Nicolas
N
Widmann
Catherine
C
Borsotto
Marc
M
Gobbi
Gabriella
G
Vaugeois
Jean-Marie
JM
Debonnel
Guy
G
Lazdunski
Michel
M
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D004351:Drug Resistance / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology; D017353:Gene Deletion; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D005473:Fluoxetine; D012701:Serotonin