High Affinity Glutamate Transport in Rat Cortical Neurons in Culture

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Vol. 53, Issue 1, 88-96, January 1998

High Affinity Glutamate Transport in Rat Cortical Neurons in Culture

Guang Jian Wang, Hye Joo Chung, Jamie Schnuer, Kara Pratt, Anthony C. Zable, Michael P. Kavanaugh and Paul A. Rosenberg

Department of Neurology and Program in Neuroscience, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115 (G.J.W., H.J.C., J.S., K.P., P.A.R.), and The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201 (A.C.Z., M.P.K.)

We assayed glutamate transport activity in cultures of rat cortical neurons containing <0.2% astrocytes. Using [³H]L-glutamate as the tracer, sodium-dependent high affinity glutamatetransport was demonstrated [K_m = 17.2 ± 2.4 µM; V_max= 3.3 ± 0.32 nmol/mg of protein/min (n = 5)]. Dihydrokainate (1mM) inhibited uptake of radioactivity by 88 ± 3% and had a K_ivalue of 65 ± 7 µM. L- $alpha$ -Aminoadipate (1 mM) inhibited uptake byonly 25 ± 4%. L-trans-2,4-Pyrrolidine dicarboxylate, L-serine-O-sulfate,and kainate potently inhibited transport activity with K_ivalues of 5.1 ± 0.3, 56 ± 6, and 103 ± 9 µM, respectively (n =3). Voltage-clamp studies of GLT1-expressing oocytes showed that,as in cortical neurons, glutamate transport was not inhibitedby L- $alpha$ -aminoadipate. Dihydrokainate was a potent inhibitor (K_i= 8 ± 1 µM), and L-serine-O-sulfate produced a GLT1-mediated currentwith a K_m value of 312 ± 33 µM. Immunoblot analysis showedthat neuronal cultures express excitatory amino acid carrier 1(EAAC1), shown previously to be relatively insensitive to dihydrokainate,plus a trace amount of GLT1, but no GLAST. These studies establishthat a major component of the glutamate transport activity ofcortical neurons is dihydrokainate sensitive and distinct fromthe previously recognized neuronal transporter excitatory aminoacid carrier 1.

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