SPECIES-DEPENDENT FUNCTIONAL-PROPERTIES OF NON-NMDA RECEPTORS EXPRESSED IN XENOPUS-LAEVIS OOCYTES INJECTED WITH MAMMALIAN AND AVIAN BRAIN MESSENGER-RNA

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 acid 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 EC(50) = 96.4 +/- 12.3 mu M; mean +/- s.e.mean), chick (87.0 +/- 8.9 mu M) or rat (88.7 +/- 4.3 mu M) 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.