Nature Neuroscience - 9, 1134 - 1141 (2006)
Published online: 13 August 2006
Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype
Catherine Heurteaux1, 6, Guillaume Lucas2, 6, Nicolas Guy1, Malika El Yacoubi3, Susanne Thümmler1, Xiao-Dong Peng2, 5, Florence Noble4, Nicolas Blondeau1, Catherine Widmann1, Marc Borsotto1, Gabriella Gobbi2, Jean-Marie Vaugeois3, Guy Debonnel2 & Michel Lazdunski1
1 Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université de Nice Sophia Antipolis, Institut Paul Hamel, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
2 Department of Psychiatry, McGill University, Montréal, Québec, Canada.
3 Faculté de Médecine et de Pharmacie, Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735-IFRMP 23, 22 Boulevard Gambetta, 76183 Rouen, France.
4 Département de Pharmacochimie Moléculaire et Structurale, Institut National de la Santé et de la Recherche Médicale U266, CNRS FRE2463, Unité de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
5 Present address: Department of Pharmacology, Ningxia Medical College, Yinchuan, Ningxia 750004, China.
6 These authors contributed equally to this work.
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. |
