Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A.
Potentiation by cyclothiazide of recombinant glutamate receptor responses in Xenopus oocytes showed absolute selectivity for AMPA versus kainate receptors. In contrast, concanavalin A strongly potentiated responses at kainate but not AMPA receptors. Rapid desensitization in HEK 293 cells transfected with AMPA receptors was blocked by cyclothiazide, but only weakly attenuated by concanavalin A. Desensitization at kainate receptors was blocked by concanavalin A but unaffected by cyclothiazide. Selective effects of these modulators following coexpression of subunits from different families suggest independent assembly of functional AMPA and kainate receptors. Northern blot analysis of mRNA for dorsal root ganglia revealed a predominant expression of GluR5, indicating that modulation of desensitization by concanavalin A but not cyclothiazide in sensory neurons accurately predicts subunit expression for native glutamate receptors.
Partin
K M
KM
Laboratory of Cellular and Molecular Neurophysiology, NICHD National Institutes of Health, Bethesda, Maryland 20892.
Patneau
D K
DK
Winters
C A
CA
Mayer
M L
ML
Buonanno
A
A
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology*; D015152:Blotting, Northern; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis
D001581:Benzothiadiazines; D003208:Concanavalin A; D046911:Macromolecular Substances; D012313:RNA; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; C004639:cyclothiazide