| A potential new target for antidepressants. Nature Neuroscience pp 1134-1141 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 different to that 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, they 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 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. Applications: Suitable for use in Western Blot. Other applications not tested. Recommended Dilution: Optimal dilutions to be determined by the researcher. Positive Control: Human brain membrane prep lysate Cellular Localization: Membrane Storage and Stability: May be stored at 4C for short-term only. For long-term storage and to avoid repeated freezing and thawing, add sterile glycerol (40-50%), aliquot and store at -20C. Aliquots are stable for at least 3 months at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer. |
