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A second pathway for antidepressants
Date:2/7/2011

Using a unique and relatively simple cell-based fluorescent assay they developed, scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC), 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," says Ehud Isacoff, a neurobiophysicist who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology. "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."

Isacoff is the corresponding author on a paper reporting the results of this study that appears in the Proceedings of the National Academy of Sciences (PNAS). The paper is titled "Optical probing of a dynamic membrane interaction that regulates the TREK1 channel." Co-authoring this paper were Guillaume Sandoz, a TREK1 specialist with France's National Center for Scientific Research at the Institute for Molecular and Cellular Physiology, and PhD student Sarah Bell, both of whom were with Isacoff's research group at the time the work was done.

Neurons in the human brain are like high-speed transistors, controlling the flow of electrical current through channels in their membranes by the opening and closing of molecular "gates" that control the flow of ions through selective pores. TREK1 is one of the most ubiqu
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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