Differential modulation of the uptake currents by redox interconversion of cysteine residues in the human neuronal glutamate transporter EAAC1

The European Journal of Neuroscience
D TrottiM A Hediger

Abstract

Control of extrasynaptic glutamate concentration in the central nervous system is an important determinant of neurotransmission and excitotoxicity. Mechanisms that modulate glutamate transporter function are therefore critical factors in these processes. The redox modulation of glutamate uptake was examined by measuring transporter-mediated electrical currents and radiolabelled amino acid influx in voltage-clamped Xenopus oocytes expressing the human neuronal glutamate transporter EAAC1. Up and down changes of the glutamate uptake currents in response to treatment with dithiothreitol and 5,5'-dithio-bis-(2-nitrobenzoic) acid (DTNB) were observed in oocytes clamped at -60 mV. The redox interconversion of cysteines induced by dithiothreitol/DTNB influenced the Vmax (Imax) of transport, while the apparent affinity for glutamate was not affected. Formation or breakdown of disulphide groups did not affect the pre-steady-state currents, suggesting that these manipulations do not interfere with the Na+ binding/unbinding and/or the charge distribution on the transporter molecule. The glutamate-evoked net uptake current of EAAC1 was composed of the inward current from electrogenic glutamate transport and the current arising from the glu...Continue Reading

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Citations

May 23, 2001·Progress in Neurobiology·N C Danbolt
Aug 1, 1997·Current Opinion in Cell Biology·M A Hediger
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May 17, 2011·Life Sciences·Joice StipurskyFlávia Carvalho Alcantara Gomes
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