Scientists find new pathway for antidepressants

Using a simple cell-based fluorescent assay they developed, scientists with the U.S. Department of Energy Lawrence Berkeley National Laboratory and the University of California, Berkeley have identified a means by which fluoxetine, the active ingredient in Prozac, suppresses the activity of the TREK1 potassium channel. TREK1 activity has been implicated in mood regulation and could be an important target for fluoxetine and other antidepressant drugs.

"Whereas the inhibiting of serotonin re-uptake remains fluoxetine's primary antidepression mechanism, many pharmacological agents have more than one target," Ehud Isacoff, a Berkeley neurobiophysicist said in a news release. "Our study shows that the inhibition of TREK1 by fluoxetine, which was found in earlier studies, is accompanied by an unbinding of the protein's C-terminal domain from the membrane. This is the first observation of the mechanism by which TREK1 might be regulated by antidepressant drugs."

"Studying what the different protein parts of an ion channel do is a huge challenge," Isacoff says. "Over the years, my group has developed techniques by which the domains of channel proteins can be labeled with site-specific fluorescent dyes. Structural rearrangements of the labeled sites in the channel can then be detected through changes in the fluorescence."

- read the Berkeley Lab release

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