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