Hu, Mu, BvApplications:
WB, ICC/IF (-), IHC (-)Host:
A potassium channel called TREK1 may represent a new target for antidepressant drugs, according to research published in the September issue of Nature Neuroscience. The channel may exert its effects through a signaling pathway in the brain that is different than what is normally targeted by most conventional antidepressants, which are thought to work by increasing the level of the neurotransmitter serotonin in the brain. Michel Lazdunski and colleagues studied mice lacking the gene for the TREK1 channel, which normally contributes to the background currents that set the resting membrane potential of neurons. In several behavioral tests used to model depression, these mice behaved as if they had been treated with an antidepressant. In addition, the mice had increased serotonergic activity, and did not release as much of the stress hormone corticosterone as normal mice in response to mild stress. Moreover, the authors report that the TREK1 channel was also directly inhibited by conventional antidepressants. The finding that mice lacking the gene for TREK1 behave as if they have been given an antidepressant suggests that small molecule blockers of the potassium channel might be effective therapeutically. If TREK1 is found to exert its antidepressant effects through a pathway independent of serotonin, it is possible that future therapies targeting TREK1 channels may be faster acting and may have fewer side effects than conventional antidepressants. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. (Nature Neuroscience pp. 1134-1141. Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thummler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois JM, Debonnel G, Lazdunski M. Published online: 13 Aug 2006 | doi:10.1038/nn1749). TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system. It is opened by polyunsaturated fatty acids and lysophospholipids. As well, it is regulated by various neurotransmitters. It has been shown that alterations in the functioning, regulation, or both of the TREK-1 channel may alter mood. TREK-1 is also activated by volatile anesthetics and has been suggested to be an important target in the action of these drugs. Therefore, this particular K+ channel emerges as a potential innovative target for developing new therapeutic agents for anesthesiology and neurology, such as antidepressants.
|Product By Gene ID
- two-pore potassium channel 1
- TWIK-related potassium channel 1
- tandem-pore-domain potassium channel TREK-1
- TREK-1 K(+) channel subunit
- subfamily K, member 2
- potassium channel, subfamily K, member 2
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