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Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants.
Sonders MS
,
Zhu SJ
,
Zahniser NR
,
Kavanaugh MP
,
Amara SG
.
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Electrophysiological and pharmacological studies of a cloned human dopamine transporter (hDAT) were undertaken to investigate the mechanisms of transporter function and the actions of drugs at this target. Using two-electrode voltage-clamp techniques with hDAT-expressing Xenopus laevis oocytes, we show that hDAT can be considered electrogenic by two criteria. (1) Uptake of hDAT substrates gives rise to a pharmacologically appropriate "transport-associated" current. (2) The velocity of DA uptake measured in oocytes clamped at various membrane potentials was voltage-dependent, increasing with hyperpolarization. Concurrent measurement of transport-associated current and substrate flux in individual oocytes revealed that charge movement during substrate translocation was greater than would be expected for a transport mechanism with fixed stoichiometry of 2 Na+ and 1 Cl- per DA+ molecule. In addition to the transport-associated current, hDAT also mediates a constitutive leak current, the voltage and ionic dependencies of which differ markedly from those of the transport-associated current. Ion substitution experiments suggest that alkali cations and protons are carried by the hDAT leak conductance. In contrast to the transport-associated functions, the leak does not require Na+ or Cl-, and DAT ligands readily interact with the transporter even in the absence of these ions. The currents that hDAT mediates provide a functional assay that readily distinguishes the modes of action of amphetamine-like "DA-releasing" drugs from cocaine-like translocation blockers. In addition, the voltage dependence of DA uptake suggests a mechanism through which presynaptic DA autoreceptor activation may accelerate the termination of dopaminergic neurotransmission in vivo.
Amara,
Neurotransmitter transporters: recent progress.
1993,
Pubmed
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994,
Pubmed
,
Xenbase
Baldessarini,
The uptake and subcellular distribution of aromatic amines in the brain of the rat.
1971,
Pubmed
Bauman,
Is drug inhibition of dopamine uptake a misinterpretation of in vitro experiments?
,
Pubmed
Bonnet,
Simultaneous evaluation by a double labelling method of drug-induced uptake inhibition and release of dopamine in synaptosomal preparation of rat striatum.
1984,
Pubmed
Buck,
Chimeric dopamine-norepinephrine transporters delineate structural domains influencing selectivity for catecholamines and 1-methyl-4-phenylpyridinium.
1994,
Pubmed
Cammack,
A GABA transporter operates asymmetrically and with variable stoichiometry.
1994,
Pubmed
Cammack,
Ions required for the electrogenic transport of GABA by horizontal cells of the catfish retina.
1993,
Pubmed
Cammack,
Channel behavior in a gamma-aminobutyrate transporter.
1996,
Pubmed
Cass,
Direct in vivo evidence that D2 dopamine receptors can modulate dopamine uptake.
1994,
Pubmed
Cerruti,
Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain.
1993,
Pubmed
Chang,
The mechanism of action of MPTP and MPP+ on endogenous dopamine release from the rat corpus striatum superfused in vitro.
1986,
Pubmed
Chen,
Thermodynamic determination of the Na+: glucose coupling ratio for the human SGLT1 cotransporter.
1995,
Pubmed
,
Xenbase
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Ciliax,
The dopamine transporter: immunochemical characterization and localization in brain.
1995,
Pubmed
Costa,
Determination of ionic permeability coefficients of the plasma membrane of Xenopus laevis oocytes under voltage clamp.
1989,
Pubmed
,
Xenbase
Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase
DeCoursey,
Voltage-activated hydrogen ion currents.
1994,
Pubmed
DeFelice,
Pore models for transporters?
1996,
Pubmed
Dorris,
Amine uptake and storage mechanisms in the corpus striatum of rat and rabbit.
1971,
Pubmed
Eliasof,
Retinal glial cell glutamate transporter is coupled to an anionic conductance.
1996,
Pubmed
Eshleman,
Characterization of a recombinant human dopamine transporter in multiple cell lines.
1995,
Pubmed
Fairman,
An excitatory amino-acid transporter with properties of a ligand-gated chloride channel.
1995,
Pubmed
,
Xenbase
Fischer,
Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model.
1979,
Pubmed
Galli,
Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants.
1995,
Pubmed
Gerhardt,
Outflow and overflow of picogram levels of endogenous dopamine and DOPAC from rat striatal slices: improved methodology for studies of stimulus-evoked release and metabolism.
1989,
Pubmed
Giros,
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter.
1996,
Pubmed
Giros,
Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter.
1992,
Pubmed
Giros,
Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters.
1994,
Pubmed
Gu,
Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence.
1994,
Pubmed
Heikkila,
Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices.
1975,
Pubmed
Isaacson,
Local and diffuse synaptic actions of GABA in the hippocampus.
1993,
Pubmed
Javitch,
[3H]mazindol binding associated with neuronal dopamine and norepinephrine uptake sites.
1984,
Pubmed
Kanner,
Mechanism of transport and storage of neurotransmitters.
1987,
Pubmed
Keller,
Evidence for the release of 1-methyl-4-phenylpyridinium (MPP+) from rat striatal neurons in vitro.
1985,
Pubmed
Krueger,
Kinetics and block of dopamine uptake in synaptosomes from rat caudate nucleus.
1990,
Pubmed
Lacey,
Neurotransmitter receptors and ionic conductances regulating the activity of neurones in substantia nigra pars compacta and ventral tegmental area.
1993,
Pubmed
Langeloh,
The mechanism of the 3H-noradrenaline releasing effect of various substrates of uptake1: multifactorial induction of outward transport.
1987,
Pubmed
Larsson,
Noise analysis of the glutamate-activated current in photoreceptors.
1996,
Pubmed
Lester,
Permeation properties of neurotransmitter transporters.
1994,
Pubmed
Liang,
Evidence for carrier-mediated efflux of dopamine from corpus striatum.
1982,
Pubmed
Lorang,
Cell-type-specific expression of catecholamine transporters in the rat brain.
1994,
Pubmed
Lukacs,
Proton conductance of the plasma membrane: properties, regulation, and functional role.
1993,
Pubmed
Mager,
Ion binding and permeation at the GABA transporter GAT1.
1996,
Pubmed
,
Xenbase
Mager,
Conducting states of a mammalian serotonin transporter.
1994,
Pubmed
,
Xenbase
Maloney,
Bacterial transporters.
1994,
Pubmed
McElvain,
A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine.
1992,
Pubmed
Meiergerd,
D2 receptors may modulate the function of the striatal transporter for dopamine: kinetic evidence from studies in vitro and in vivo.
1993,
Pubmed
Nestler,
Drug addiction: a model for the molecular basis of neural plasticity.
1993,
Pubmed
Nirenberg,
The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons.
1996,
Pubmed
Parent,
Electrogenic properties of the cloned Na+/glucose cotransporter: I. Voltage-clamp studies.
1992,
Pubmed
,
Xenbase
Parker,
Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. I. Release in the absence of vesicular transmitter stores.
1986,
Pubmed
Parsons,
Co-administration of the D2 antagonist pimozide inhibits up-regulation of dopamine release and uptake induced by repeated cocaine.
1993,
Pubmed
Pifl,
Dopamine transporter expression confers cytotoxicity to low doses of the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium.
1993,
Pubmed
Pifl,
Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter.
1995,
Pubmed
Pristupa,
Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding.
1994,
Pubmed
Pulvirenti,
Dopamine receptor agonists, partial agonists and psychostimulant addiction.
1994,
Pubmed
Raiteri,
Dopamine can be released by two mechanisms differentially affected by the dopamine transport inhibitor nomifensine.
1979,
Pubmed
Raiteri,
Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine.
1977,
Pubmed
Risso,
Sodium-dependent GABA-induced currents in GAT1-transfected HeLa cells.
1996,
Pubmed
Ritz,
Cocaine receptors on dopamine transporters are related to self-administration of cocaine.
1987,
Pubmed
Rollema,
Brain dialysis in conscious rats reveals an instantaneous massive release of striatal dopamine in response to MPP+.
1986,
Pubmed
Rudnick,
From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters.
1993,
Pubmed
Seiden,
Amphetamine: effects on catecholamine systems and behavior.
1993,
Pubmed
Sesack,
Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets.
1994,
Pubmed
Sirinathsinghji,
Dopamine-releasing action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) in the neostriatum of the rat as demonstrated in vivo by the push-pull perfusion technique: dependence on sodium but not calcium ions.
1988,
Pubmed
Sonders,
Channels in transporters.
1996,
Pubmed
Steinberg,
Effects of desmethylimipramine and cocaine on the uptake, retention and metabolism of H3-tyramine in rat brain slices.
1970,
Pubmed
Sulzer,
Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport.
1995,
Pubmed
Sulzer,
Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action.
1990,
Pubmed
Turner,
Stoichiometry of cotransport systems.
1985,
Pubmed
Umbach,
Intestinal Na+/glucose cotransporter expressed in Xenopus oocytes is electrogenic.
1990,
Pubmed
,
Xenbase
Vandenberg,
Constitutive ion fluxes and substrate binding domains of human glutamate transporters.
1995,
Pubmed
,
Xenbase
Vandenbergh,
A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs.
1992,
Pubmed
Wadiche,
Ion fluxes associated with excitatory amino acid transport.
1995,
Pubmed
,
Xenbase
Wall,
Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux.
1995,
Pubmed
White,
Synaptic regulation of mesocorticolimbic dopamine neurons.
1996,
Pubmed
Wise,
Addictive drugs and brain stimulation reward.
1996,
Pubmed
Yung,
Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy.
1995,
Pubmed
Zaczek,
Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport.
1991,
Pubmed
