Flux coupling in the human serotonin transporter.
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) (> or =10 microM), but is not restricted to this regime of external 5HT.
Adams
Scott V
SV
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37232, USA.
DeFelice
Louis J
LJ
D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D007668:Kidney / Q000196:embryology / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D016062:Porosity; D011985:Receptors, Serotonin / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D015398:Signal Transduction / Q000502:physiology; D027981:Symporters / Q000502:physiology*
D002352:Carrier Proteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D012701:Serotonin