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Ionic currents in the human serotonin transporter reveal inconsistencies in the alternating access hypothesis.
Adams SV, DeFelice LJ.
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We have investigated the conduction states of human serotonin transporter (hSERT) using the voltage clamp, cut-open frog oocyte method under different internal and external ionic conditions. Our data indicate discrepancies in the alternating access model of cotransport, which cannot consistently explain substrate transport and electrophysiological data. We are able simultaneously to isolate distinct external and internal binding sites for substrate, which exert different effects upon currents conducted by hSERT, in contradiction to the alternating access model. External binding sites of coupled Na ions are likewise simultaneously accessible from the internal and external face. Although Na and Cl are putatively cotransported, they have opposite effects on the internal face of the transporter. Finally, the internal K ion does not compete with internal 5-hydroxytryptamine for empty transporters. These data can be explained more readily in the language of ion channels, rather than carrier models distinguished by alternating access mechanisms: in a channel model of coupled transport, the currents represent different states of the same permeation path through hSERT and coupling occurs in a common pore.
Adams,
Flux coupling in the human serotonin transporter.
2002, Pubmed
Adams,
Flux coupling in the human serotonin transporter.
2002,
Pubmed Blakely,
Molecular physiology of norepinephrine and serotonin transporters.
1994,
Pubmed Bunin,
Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: an investigation of extrasynaptic transmission.
1998,
Pubmed Cao,
Amino acid residues that control pH modulation of transport-associated current in mammalian serotonin transporters.
1998,
Pubmed
,
Xenbase Cao,
H+ permeation and pH regulation at a mammalian serotonin transporter.
1997,
Pubmed
,
Xenbase Chen,
Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters.
2001,
Pubmed Chen,
Thermodynamic determination of the Na+: glucose coupling ratio for the human SGLT1 cotransporter.
1995,
Pubmed
,
Xenbase Chen,
Fast voltage clamp discloses a new component of presteady-state currents from the Na(+)-glucose cotransporter.
1996,
Pubmed
,
Xenbase Coady,
Electrogenic amino acid exchange via the rBAT transporter.
1994,
Pubmed
,
Xenbase Coady,
rBAT is an amino acid exchanger with variable stoichiometry.
1996,
Pubmed
,
Xenbase Costa,
Improved technique for studying ion channels expressed in Xenopus oocytes, including fast superfusion.
1994,
Pubmed
,
Xenbase Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase De Felice,
Serotonin and norepinephrine transporters: possible relationship between oligomeric structure and channel modes of conduction.
2001,
Pubmed
,
Xenbase DeFelice,
Single-file diffusion and neurotransmitter transporters: Hodgkin and Keynes model revisited.
2001,
Pubmed Eddahibi,
Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension.
2001,
Pubmed Elsner,
Poor quality of oocytes from Xenopus laevis used in laboratory experiments: prevention by use of antiseptic surgical technique and antibiotic supplementation.
2000,
Pubmed
,
Xenbase Galli,
Norepinephrine transporters have channel modes of conduction.
1996,
Pubmed Galli,
Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel.
1997,
Pubmed
,
Xenbase Galli,
Patch-clamp and amperometric recordings from norepinephrine transporters: channel activity and voltage-dependent uptake.
1998,
Pubmed Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase Gu,
Ion coupling stoichiometry for the norepinephrine transporter in membrane vesicles from stably transfected cells.
1996,
Pubmed Gu,
Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence.
1994,
Pubmed Hilgemann,
GAT1 (GABA:Na+:Cl-) cotransport function. Database reconstruction with an alternating access model.
1999,
Pubmed
,
Xenbase HODGKIN,
The potassium permeability of a giant nerve fibre.
1955,
Pubmed Ingram,
Arachidonic acid stimulates a novel cocaine-sensitive cation conductance associated with the human dopamine transporter.
2000,
Pubmed
,
Xenbase Iversen,
Role of transmitter uptake mechanisms in synaptic neurotransmission.
1971,
Pubmed Jardetzky,
Simple allosteric model for membrane pumps.
1966,
Pubmed Kaneko,
Cut-open recording techniques.
1998,
Pubmed
,
Xenbase Keyes,
Coupling of transmembrane proton gradients to platelet serotonin transport.
1982,
Pubmed Kuruma,
Dynamics of calcium regulation of chloride currents in Xenopus oocytes.
1999,
Pubmed
,
Xenbase Li,
Voltage-dependent transient currents of human and rat 5-HT transporters (SERT) are blocked by HEPES and ion channel ligands.
2002,
Pubmed
,
Xenbase Lin,
Single-channel currents produced by the serotonin transporter and analysis of a mutation affecting ion permeation.
1996,
Pubmed
,
Xenbase Loo,
Role of Cl- in electrogenic Na+-coupled cotransporters GAT1 and SGLT1.
2000,
Pubmed
,
Xenbase Lu,
GAT1 (GABA:Na+:Cl-) cotransport function. Steady state studies in giant Xenopus oocyte membrane patches.
1999,
Pubmed
,
Xenbase Mager,
Conducting states of a mammalian serotonin transporter.
1994,
Pubmed
,
Xenbase Mager,
Steady states, charge movements, and rates for a cloned GABA transporter expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase Nelson,
Coupling between platelet 5-hydroxytryptamine and potassium transport.
1979,
Pubmed Ni,
A lithium-induced conformational change in serotonin transporter alters cocaine binding, ion conductance, and reactivity of Cys-109.
2001,
Pubmed
,
Xenbase Petersen,
Ionic interactions in the Drosophila serotonin transporter identify it as a serotonin channel.
1999,
Pubmed
,
Xenbase Quick,
Incubation with horse serum increases viability and decreases background neurotransmitter uptake in Xenopus oocytes.
1992,
Pubmed
,
Xenbase Ramamoorthy,
Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.
1993,
Pubmed Ramsey,
Serotonin transporter function and pharmacology are sensitive to expression level: evidence for an endogenous regulatory factor.
2002,
Pubmed
,
Xenbase Rudnick,
Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets.
1977,
Pubmed Rudnick,
Platelet 5-hydroxytryptamine transport, an electroneutral mechanism coupled to potassium.
1978,
Pubmed Rudnick,
Ion-coupled neurotransmitter transport: thermodynamic vs. kinetic determinations of stoichiometry.
1998,
Pubmed Rudnick,
From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters.
1993,
Pubmed Sitte,
Quantitative analysis of inward and outward transport rates in cells stably expressing the cloned human serotonin transporter: inconsistencies with the hypothesis of facilitated exchange diffusion.
2001,
Pubmed Sitte,
Characterization of carrier-mediated efflux in human embryonic kidney 293 cells stably expressing the rat serotonin transporter: a superfusion study.
2000,
Pubmed Sonders,
Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants.
1997,
Pubmed
,
Xenbase Sonders,
Channels in transporters.
1996,
Pubmed Stefani,
Cut-open oocyte voltage-clamp technique.
1998,
Pubmed
,
Xenbase Stühmer,
Electrophysiologic recordings from Xenopus oocytes.
1998,
Pubmed
,
Xenbase