AMPA, kainate, and quisqualate activate a common receptor-channel complex on embryonic chick motoneurons.
The actions of the putative quisqualate-selective agonist DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were examined in identified embryonic chick motoneurons using gigaseal recording techniques and compared with properties of the selective non-NMDA excitatory amino acid agonists kainate and quisqualate. Pressure application of AMPA induces an inward going current when neurons are voltage-clamped at negative membrane potentials. The current-voltage relationship for this response is linear with reversal near 0 mV. Over the range of 1 microM-10 mM, the AMPA-induced current is dose-dependent with an ED50 of 40 microM. AMPA currents are insensitive to the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate, and the putative quisqualate selective blocker, glutamate diethyl ester, but are partially inhibited by kynurenic acid. In competition experiments, applications of saturating concentrations of AMPA and either kainate or quisqualate produce responses intermediate between the response to either agonist alone, indicating commonality in the mechanism of these agents. Applications of AMPA with the NMDA-selective agonist aspartate give an additive response. Analysis of current fluctuations indicates that AMPA, quisqualate, and kainate gate a channel with a primary conductance near 20 pS. Differences in maximal macroscopic current evoked by saturating concentrations of AMPA, kainate, and quisqualate cannot be explained by differences in mean channel open time as the most efficacious agonist, kainate, has the shortest channel open time (AMPA = 5.9 +/- 0.4 msec, kainate = 2.7 +/- 0.1 msec, quisqualate = 5.0 +/- 0.5 msec). Rather, kainate induces a greater frequency of channel opening. This finding contrasts with results obtained at the nicotinic ACh receptor, where the most efficacious agonists have the longest mean channel open time. Our results suggest that AMPA acts at the same receptor-channel complex as kainate and quisqualate on chick motoneurons and support the hypothesis that only 2 classes of excitatory amino acid receptor complexes exist in this preparation.
Zorumski
C F
CF
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri.
Yang
J
J
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002642:Chick Embryo; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology*; D009046:Motor Neurons / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D007473:Ion Channels; D010069:Oxadiazoles; D010080:Oxazoles; D011956:Receptors, Cell Surface; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid