ACTIVATION OF A METABOTROPIC GLUTAMATE-RECEPTOR INCREASES INTRACELLULAR CALCIUM CONCENTRATIONS IN NEURONS OF THE AVIAN COCHLEAR NUCLEUS

Metabotropic glutamate receptors have been shown to stimulate phosphat idylinositol metabolism, and subsequently liberate Ca2+ from intracell ular stores, in a variety of tissue and cell types. We previously demo nstrated that glutamate could stimulate phosphatidylinositol metabolis m, generating inositol-1,4,5-trisphosphate (IP3), in isolated cochlear nucleus tissue from the chick. Using the calcium indicator dye fura-2 and ratiometric fluorescent imaging, this study examined the ability of glutamate and its analogs to liberate Ca2+ from intracellular store s of neurons of the avian cochlear nucleus, and qualitatively characte rized the pharmacological profile of such an action. In normal, Ca2+-c ontaining medium, glutamate, kainate (KA), ha-amino-3-hydroxy-5-methyl -isoxazole-4-propionate (AMPA), NMDA, quisqualate (QUIS), and (+/-)-am inocyclopentane-trans-dicarboxylate (ACPD) elicited increases in intra cellular calcium concentrations ([Ca2+](i)). In the absence of externa l Ca2+, glutamate, quisqualate, and ACPD evoked increases in [Ca2+](i) . In normal medium, the ionotropic glutamate receptor antagonist 6-cya no-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA receptor antagonis t 2-amino-5-phosphonovalerate (APV) attenuated but did not abolish the glutamate-evoked response and had no effect on the ACPD-evoked respon se. The putative metabotropic glutamate receptor antagonist 2-amino-3- phosphonopropionate (AP3) was without effect on the glutamate- and ACP D-evoked increases in [Ca2+](i) in Ca2+-free medium. We conclude that a metabotropic glutamate receptor (mGluR) is present on cochlear nucle us neurons and is able to stimulate the phosphatidylinositol metabolis m-Ca2+ signal transduction cascade.