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The Journal of Neuroscience, January 1, 2000, 20(1):251-258

AMPA-Kainate Subtypes of Glutamate Receptor in Rat Cerebral Microglia

Mami Noda1, Hiroshi Nakanishi2, Junichi Nabekura1, and Norio Akaike1

1 Laboratory of Cellular and System Physiology, Graduate School of Medical Science, and 2 Department of Pharmacology, Faculty of Dentistry, Kyushu University, Fukuoka 812-8582, Japan

Microglial cells were isolated from rat cerebral cortex, and kainate (KA)-induced inward current was measured at a holding potential of -40 or -60 mV. 6-Cyano-7-nitroquinoxaline-2, 3-dione-sensitive KA-induced currents increased with increasing KA concentration. The half-activation concentration and Hill coefficient were 3.3 × 10-4 M and 1.4, respectively. Although glutamate (Glu) and AMPA-induced currents were much smaller than that induced by KA, all KA-, Glu-, and AMPA-induced currents were greatly and consistently enhanced in the presence of cyclothiazide (CTZ). On the other hand, KA-induced currents were much less sensitive to potentiation by concanavain A, suggesting that the KA-induced response in rat microglia is predominantly mediated by AMPA-preferring receptors (subunits GluR1-GluR4). The current-voltage relationships of KA- and AMPA-CTZ-induced currents were almost linear or slightly outward rectifying. The reversal potential of KA-induced current shifted to negative potentials (from +4 to -40 mV) on switching from high Na+ to high Ca2+ external solution, indicating the low Ca2+ permeability through the AMPA-KA receptor channel complexes. AMPA-KA receptor expression was studied with immunohistochemistry and reverse transcription-PCR, from which GluR2, GluR3, GluR4, and GluR5 were identified. Lower levels of mRNAs for GluR7 and KA-1-KA-2 were also indicated. Finally, activation of these receptors with KA or Glu significantly enhanced the production of tumor necrosis factor-alpha . These results suggest that primary cultured rat microglia possesses functional Glu receptor, which may mediate neuron to microglia communication in the physiological and pathological states.

Key words: microglia; whole-cell patch clamp; kainate; glutamate; AMPA; cyclothiazide; reverse transcription-PCR; tumor necrosis factor-alpha


Copyright © 2000 Society for Neuroscience  0270-6474/0/201251-08$05.00/0


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