γ- d-glutamylaminomethyl sulfonic acid (GAMS) distinguishes subtypes of glutamate receptor in the chick cochlear nucleus (nuc. magnocellularis)

Abstract

Because kainic acid (KA) is more potent than other excitatory amino acids (EAAs) in affecting synaptic transmission in the cochlear nucleus, previous reports have concluded that primary afferent neurotransmission to the cochlear nucleus in birds and mammals is mediated by KA-preferring non- n-methyl- d-aspartate (non-NMDA) EAA receptors. Since this conclusion is at odds with a number of studies suggesting that rapid excitatory neurotransmission in the CNS is mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring non-NMDA receptors, we re-examined the pharmacology of synaptic transmission between the cochlear nerve and nucleus magnocellularis (NM) in chickens, using bath application of drugs and recording of field potentials evoked in NM by electrical stimulation of the cochlear nerve in vitro. A series of EAA agonists produced complete, concentration-dependent and reversible suppression of postsynaptic responses: the order of potency was domoic acid ( DO) > KA > AMPA ⪢ quisqualic acid ⪢ l- glutamic acid (Glu). Three quinoxalinedione antagonists of non-6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione NMDA receptors also produced complete, concentration-dependent and reversible suppression of postsynaptic responses in NM without affecting the presynaptic action potential; the half-maximal inhibitory concentrations (IC 50's) were 2.7 ± 0.4 μM for 6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione (NBQX), 5.3 ± 0.1 μM for 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 10.6 ± 1.2 μM for 6,7-dinitroquinoxaline-2,3-dione (DNQX). At concentrations that were without effect on postsynaptic responses elicited by stimulation of the cochlear nerve, γ- d-glutamylaminomethyl sulfonic acid (GAMS), a competitive glutamate antagonist that has shown some selectivity for KA receptors in mammalian spinal cord, significantly reversed the suppression of postsynaptic responses produced by KA or AMPA but not by Glu. Taken together with other relevant experimental findings, these data suggest that 1) GAMS-sensitive and GAMS-insensitive non-NMDA receptors exist in NM and 2) the receptors mediating synaptic transmission in NM are AMPA-preferring and GAMS-insensitive.