Journal
BIOPHYSICAL JOURNAL
Volume 83, Issue 6, Pages 3268-3282Publisher
BIOPHYSICAL SOCIETY
DOI: 10.1016/S0006-3495(02)75328-9
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Funding
- NINDS NIH HHS [NS 34075] Funding Source: Medline
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The serotonin (5-hydroxytryptamine; 5HT) transporter (SERT) catalyzes the movement of 5HT across cellular membranes. In the brain, SERT clears 5HT from extracellular spaces, modulating the strength and duration of serotonergic signaling. SERT is also an important pharmacological target for antidepressants and drugs of abuse. We have studied the flux of radio-labeled 5HT through the transporter stably expressed in HEK-293 cells. Analysis of the time course of net transport, the equilibrium 5HT gradient sustained, and the ratio of the unidirectional influx to efflux of 5HT indicate that mechanistically, human SERT functions as a 5HT channel rather than a classical carrier. This is especially apparent at relatively high [5HT](out) (greater than or equal to10 muM), but is not restricted to this regime of external 5HT.
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