Glutamatergic and GABAergic agonists increase [Ca2+]i in avian cochlear nucleus neurons

Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are stimulated by glutamate, released from the auditory nerve, and GABA, released from both interneurons surrounding NM and from cells located in the superior olivary nucleus. In this study, the Ca²⁺ indicator dye Fura-2 was used to measure Ca²⁺ responses in NM stimulated by glutamate- and GABA-receptor agonists using a chicken brainstem slice preparation. Glutamatergically stimulated Ca²⁺ responses were evoked by kainic acid (KA), α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), and N-methyl-D -aspartate (NMDA). KA- and AMPA-stimulated changes in Ca²⁺]_i were also produced in NM neurons stimulated in the presence of nifedipine, an L-type Ca²⁺ channel blocker, suggesting that KA- and AMPA-stimulated changes in Ca²⁺]_i were carried by Ca²⁺-permeable receptor channels. Significantly smaller changes in Ca²⁺]_i were produced by NMDA. When neurons were stimulated in an alkaline (pH 7.8) superfusate, NMDA responses were potentiated. KA- and AMPA-stimulated responses were not affected by pH. Several agents known to stimulate metabotropic receptors in other systems were tested on NM neurons bathed in a Ca²⁺ free-EGTA–buffered media, including l -cysteine sulfinic acid (L-CSA), trans-azetidine dicarboxylic acid (t-ADA), trans-aminocyclopentanedicarboxylic acid (t-ACPD), and homobromoibotenic acid (HBI). The only agent to reliably and dose-dependently increase Ca²⁺]_i was HBI, an analog of ibotenate. GABA also stimulated increases in Ca²⁺]_i in NM neurons. GABA-stimulated responses were reduced by agents that block voltage-operated channels and by agents that inhibit Ca²⁺ release from intracellular stores. Whereas GABA-A receptor agonist produced increases in Ca²⁺]_i GABA-B and GABA-C receptor agonists had no effect. There appear to be several ways for Ca²⁺]_i to increase in NM neurons. Presumably, each route represents a means by which Ca²⁺ can alter cellular processes. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 321–337, 1998