Species-dependent functional properties of non-NMDA receptors expressed in Xenopus laevis oocytes injected with mammalian and avian brain mRNA.
1. Species-dependent variation in the functional properties of non-NMDA receptors was investigated by intracellular recording in Xenopus laevis oocytes injected with rat, chick and calf brain mRNA. 2. In all mRNA-injected oocytes, kainic acid (KA), domoic acid (Dom) and 5-bromowillardiine (BrW) evoked large, maintained membrane currents, in contrast to the smaller, desensitizing responses elicited by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid (QA) and L-glutamic acid (L-Glu). Dose-response curves for KA in oocytes injected with calf (EC50 = 96.4 +/- 12.3 microM; mean +/- s.e. mean), chick (87.0 +/- 8.9 microM) or rat (88.7 +/- 4.3 microM) brain mRNA were similar. 3. Current-voltage (I-V) relationships determined with KA inwardly rectified in oocytes injected with calf or chick mRNA; whereas, outward rectification was observed in oocytes injected with rat brain mRNA. 4. In oocytes injected with rat brain mRNA, AMPA antagonized responses evoked by KA in a competitive manner. The absolute amplitudes of KA and AMPA responses in the same oocytes were significantly correlated, which is consistent with both agonists acting on the same receptor-ionophore complex. 5. In contrast, in oocytes injected with calf or chick brain mRNA, AMPA (QA and L-Glu) antagonized the response evoked by KA in a non-competitive manner. The response amplitudes of KA compared to AMPA, QA or L-Glu in the same oocytes were not correlated suggesting discrete receptor-ionophores. 6. This study favours the existence of distinct non-NMDA receptor subtypes that are equi-sensitive to KA. The expressed receptors from different species of mRNA may be distinguished by their voltage sensitivities and the type of antagonism exerted by AMPA on KA-activated responses. Our observations may reflect further heterogeneity of non-NMDA receptors in the central nervous system of different vertebrate species.
Bowie
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Department of Pharmacology, School of Pharmacy, University of London.
Smart
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D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000235:genetics*; D002417:Cattle; D002645:Chickens; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D009865:Oocytes / Q000502:physiology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000494:pharmacology*; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid