SERINE-O-SULFATE TRANSPORT BY THE HUMAN GLUTAMATE TRANSPORTER, EAAT2

1 Expression of the recombinant human excitatory amino aid transporter s, EAAT1 and EAAT2, in Xenopus laevis oocytes allows electrogenic tran sport to be studied under voltage clamp conditions. 2 We have investig ated the transport of the pharmacological substrate, L-serine-O-sulpha te transport by EAAT1 and EAAT2. The EC50 values for L-serine-O-sulpha te transport by EAAT2 showed a steep voltage-dependence, increasing fr om 152+/-11 mu M at -100 mV to 1930+/-160 mu M at 0 mV. In contrast to EAAT2, EC50 values for L-serine-O-sulphate transport by EAAT1 were re latively constant over the membrane potential range of -100 mV to 0 mV . The EC50 values for L-glutamate and D-aspartate transport, by EAAT2, were also relatively constant over this membrane potential range. 3 C hloride ions modulated the voltage-dependent changes in EC50 values fo r transport by EAAT2. This effect was most apparent for L-serine-O-sul phate transport, and to a lesser extent for L-glutamate and not at all for D-aspartate transport by EAAT2. 4 Extracellular sodium and proton concentrations also modulated the voltage-dependence of L-serine-O-su lphate EC50 values for EAAT2. 5 We speculate that these different prop erties of L-serine-O-sulphate transport by EAAT2 compared to other sub strates may be due to the much stronger acidity of the sulphate group of L-serine-O-sulphate compared to carboxyl groups of L-glutamate or D -aspartate. 6 These results highlight some of the differences in the w ay different glutamate transporter subtypes transport substrates. This may be used to understand further the transport process and develop s ubtype selective inhibitors of glutamate transport.