Fluctuation analysis of norepinephrine and serotonin transporter currents.
Findings from an electrophysiological analysis of neurotransmitter transporters show that transmitter-induced currents are associated with these transporters: For charged transmitters, such as NE and 5-HT, a fraction of the total current is carried by the transmitter itself; however, the transmitter also induces an extra current in analogy to an ligand-gated ion channel. An additional conductance not discussed in this article is the so-called leak, in which neurotransmitter transporters generate an ionic current in the absence of transmitter. Using a combination of flux measurements, voltage clamp, and fluctuation analysis has shown that, for norepinephrine and serotonin transporters, the transmitter-induced current greatly exceeds the transmitter current. Such data can provide an exact measure of the ratio of these charge movements to transmitter translocation at the molecular level, suggesting new strategies to understand neurotransmitter transporters.
DeFelice
L J
LJ
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6600, USA.
Galli
A
A
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026901:Membrane Transport Proteins; D008956:Models, Chemical; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016716:PC12 Cells; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011994:Recombinant Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D012701:Serotonin; D009638:Norepinephrine