Zinc inhibition of group I mGluR-mediated calcium homeostasis in auditory neurons.
Zinc is widely distributed in the central nervous system (CNS), it functions normally as a synaptic modulator, and it contributes to neuronal death under pathologic conditions. Zinc colocalizes with glutamate in excitatory synapses, and the presence of zinc is well characterized in the synapses of the auditory system. Since chick cochlear nucleus neurons depend upon synaptic activation of metabotropic glutamate receptors (mGluRs) for maintenance and survival, the goal of this study was to determine (1) if zinc is released from the eighth nerve calyces onto nucleus magnocellularis (NM) neurons in the chick cochlear nucleus, and, if so, (2) what effect it has on group I mGluR-mediated calcium homeostasis of these neurons. Using in vitro slices and a fluorescent dye relatively specific to vesicularized zinc, we show that zinc is indeed localized to the presynaptic calyces and is released upon nerve stimulation or KCl depolarization. Experiments employing fura-2 calcium imaging show that zinc inhibits group I mGluR release of calcium from internal stores of NM neurons and disrupts activity-dependent calcium homeostasis in a manner identical to the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine. The mGluR1-specific antagonist 7-hydroxyiminocyclopropan-[b]chromen-la-carboxylic acid ethyl ester did not affect release of calcium from stores by the nonspecific mGluR agonist aminocyclopentane dicarboxylic acid, nor did it affect activity-dependent calcium homeostasis. We conclude that zinc is present in and released from the glutamatergic eighth nerve calcyes. The presence of zinc inhibits mGluR5, a major component of calcium homeostasis of NM neurons, and plays a modulatory role in the activity-dependent, mGluR-mediated calcium homeostasis of auditory neurons.
Zirpel
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Department of Neurobiology & Anatomy, Building 530, Room 417, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA. zlance@neuro.utah.edu
Parks
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TN
D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D004594:Electrophysiology; D006706:Homeostasis / Q000187:drug effects*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013377:Substantia Innominata / Q000187:drug effects / Q000378:metabolism; D000159:Vestibulocochlear Nerve / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D015032:Zinc; D002118:Calcium