title: Glutamate regulates IP3-type and CICR stores in the avian cochlear nucleus.
abstract: Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are activated by glutamate released from auditory nerve terminals. If this stimulation is removed, the intracellular calcium ion concentration ([Ca2+]i) of NM neurons rises and rapid atrophic changes ensue. We have been investigating mechanisms that regulate [Ca2+]i in these neurons based on the hypothesis that loss of Ca2+ homeostasis causes the cascade of cellular changes that results in neuronal atrophy and death. In the present study, video-enhanced fluorometry was used to monitor changes in [Ca2+]i stimulated by agents that mobilize Ca2+ from intracellular stores and to study the modulation of these responses by glutamate. Homobromoibotenic acid (HBI) was used to stimulate inositol trisphosphate (IP3)-sensitive stores, and caffeine was used to mobilize Ca2+ from Ca2+-induced Ca2+ release (CICR) stores. We provide data indicating that Ca2+ responses attributable to IP3- and CICR-sensitive stores are inhibited by glutamate, acting via a metabotropic glutamate receptor (mGluR). We also show that activation of C-kinase by a phorbol ester will reduce HBI-stimulated calcium responses. Although the protein kinase A accumulator, Sp-cAMPs, did not have an effect on HBI-induced responses. CICR-stimulated responses were not consistently attenuated by either the phorbol ester or the Sp-cAMPs. We have previously shown that glutamate attenuates voltage-dependent changes in [Ca2+]i. Coupled with the present findings, this suggests that in these neurons mGluRs serve to limit fluctuations in intracellular Ca2+ rather than increase [Ca2+]i. This system may play a role in protecting highly active neurons from calcium toxicity resulting in apoptosis.
authors: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors: B M
authors: BM
authors: Kato
authors: E W
authors: EW
authors: Rubel
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D017626:Cochlear Nucleus / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D001565:Benzoates; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D013873:Thionucleotides; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D012433:Ryanodine; C016957:adenosine-3',5'-cyclic phosphorothioate; D007051:Ibotenic Acid; D002110:Caffeine; D018698:Glutamic Acid; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003545:Cysteine; D000409:Alanine; D002118:Calcium; D005998:Glycine; D016257:Fura-2; C013461:cysteine sulfinic acid