A Model for GABA and Glutamic Acid Transport by Cortical Synaptosomes

Dd, Wheeler

doi:10.1159/000137426

Cited by 25 publications

(7 citation statements)

References 17 publications

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“…It seems likely that this may be so. Uptake of acidic amino acids is via a sodium- [ 12] and membrane potential-dependent [ 13] transporter very similar to that which we [un-publ. data] and others [11] find for DA.…”

Section: Discussionsupporting

confidence: 62%

Effects of Veratridine and Cocaine on the Kinetics of Synaptosomal Dopamine Release

Wheeler¹,

Chapman²,

Ondo³

1993

Pharmacology

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Following preloading of striatal synaptosomes with ³H-dopamine (DA), the kinetics of release have been followed for a 60-min incubation period. DA appears to be totally releasable under both depolarizing (veratridine) and nondepolarizing conditions. Cocaine has no significant effect on release under either condition. Release is consistent with a model consisting of two parallel, linear compartments (when plotted as a log function). It is proposed that the slower compartment might represent the operation of the DA transporter, while the faster compartment might represent vesicular release.

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Section: Discussionsupporting

confidence: 62%

Effects of Veratridine and Cocaine on the Kinetics of Synaptosomal Dopamine Release

Wheeler¹,

Chapman²,

Ondo³

1993

Pharmacology

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“…This article presents evidence for the stoichiometric relationships among the components required for DA uptake but does not provide enough information to attempt to model, quantitatively, the transport system and, in particular, how each of the various components might affect the rates of transport. To make determinations of this kind additional information will be needed including measurement of unidirectional efflux and its dependence on intracellular and extracellular ions and DA, measurement of the effects of intracellular ions on unidirectional influx, determination of net DA uptake uncomplicated by the presence of dopaminergic synaptic vesicles, and a more accurate evaluation of the effect of the membrane potential on the unidirectional rates of DA transport and on net DA transport (for theoretical analyses of other transmitter systems, see Blaustein and King, 1976;Kanner, 1978;Wheeler, 1980;Nelson and Blaustein, 1982). Many of these studies could be performed on membrane vesicles derived from osmotically shocked synaptosomes (Schoemaker and Nickolson, 1982).…”

Section: Discussionmentioning

confidence: 99%

Kinetics and Block of Dopamine Uptake in Synaptosomes from Rat Caudate Nucleus

Krueger

1990

Journal of Neurochemistry

135

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The dopamine (DA) uptake system in mammalian nerve terminals was studied by measuring the unidirectional influx of tritiated DA into synaptosomes prepared from rat caudate nucleus. Two distinct time-dependent components of DA uptake were observed. The principal component was saturable with respect to DA concentration, required both external Na and Cl, and was competitively blocked by micromolar concentrations of the psychotropic agents cocaine, benztropine, nomifensine, amphetamine, and methamphetamine. This principal component of uptake has the properties expected for a carrier-mediated transport system. The second component, which accounted for about 10-30% of the DA uptake at 2 microM DA, was not saturable, and was independent of external Na, Cl, and blockers of the carrier-mediated system. The saturable, Na-dependent component had an apparent Km(DA) of about 0.5 microM. The dependence of DA uptake on external Na was sigmoid [Hill coefficient = 2; Ka(Na) = 45 mM] whereas the dependence on Cl was best described by a rectangular hyperbola [Ka(Cl) = 15 mM]. Depolarizing conditions (elevated external K) reduced the rate of DA influx. The data are consistent with a carrier-mediated DA transport mechanism in which each DA molecule entering the nerve terminal via the carrier is accompanied by two or more Na ions and one Cl ion in a rheogenic process carrying one or more net positive charges into the cell. Net, concentrative accumulation of DA inside nerve terminals may be accomplished by utilizing the Na electrochemical gradient to drive DA against its electrochemical gradient via this carrier system.

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“…However, it may be that an appreciable effect of Na+ on substrate affinity occurs at concentrations below those used in our study. Wheeler (1980) and Wheeler and Graves (1983) have proposed models for the Na+-dependent uptake of glutamate and GABA in which the affinity between glutamate and its carrier decreases approximately fivefold as Na' is reduced to zero, whereas the affinity between GABA and its carrier increases moderately as Na+ is reduced to zero.…”

Section: Discussionmentioning

confidence: 99%

Ion Dependence of Neurotransmitter Uptake: Inhibitory Effects of Ion Substitutes

Shank

Schneider

Tighe

1987

Journal of Neurochemistry

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Several ions commonly used as substitutes for Na+ or Cl- were found to inhibit directly the high-affinity uptake of norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid, but not glutamate or glutamine. When Na+ was partially replaced by any of several different cations or sucrose the uptake of all neurotransmitters studied except that of serotonin was reduced more than could be accounted for by just the inhibitory effect of the cation substitute. In contrast, when Cl- was partially replaced by any of several anions only the uptake of dopamine was reduced more than could be accounted for by the inhibitory effect of the anion substitute. These results suggest that for most neurotransmitters the electrochemical potential for Na+, but not for Cl-, contributes to the uptake driving force. When either Na+ or Cl- was totally replaced by an ion substitute or by sucrose the high-affinity uptake was virtually abolished, an exception being that glutamate uptake was not affected when isethionate was substituted for Cl-. The lack of uptake in the absence of either Na+ or Cl- may reflect a specific role for these ions in either increasing the affinity between the substrate and the carrier, or facilitating the translocation process. Alternatively, the transport carriers may undergo a nonspecific conformational change to an inactive form in the absence of Na+ or Cl-. A partial substitution of Na+ with Li+ or sucrose differentially affected the kinetics of uptake in that replacement with Li+, but not sucrose, usually resulted in a marked increase in the Km values.(ABSTRACT TRUNCATED AT 250 WORDS)

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A Model for GABA and Glutamic Acid Transport by Cortical Synaptosomes

Cited by 25 publications

References 17 publications

Effects of Veratridine and Cocaine on the Kinetics of Synaptosomal Dopamine Release

Effects of Veratridine and Cocaine on the Kinetics of Synaptosomal Dopamine Release

Kinetics and Block of Dopamine Uptake in Synaptosomes from Rat Caudate Nucleus

Ion Dependence of Neurotransmitter Uptake: Inhibitory Effects of Ion Substitutes

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