ryanodine and cysteine-sulfinic-acid

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.

Topics: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Alanine; Animals; Benzoates; Caffeine; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Chelating Agents; Chick Embryo; Cochlear Nucleus; Cyclic AMP; Cycloleucine; Cysteine; Egtazic Acid; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Fluorescent Dyes; Fura-2; Gallic Acid; Glutamic Acid; Glycine; Ibotenic Acid; Inositol 1,4,5-Trisphosphate Receptors; Ion Channel Gating; Neurons; Neuroprotective Agents; Neurotransmitter Agents; Patch-Clamp Techniques; Phosphodiesterase Inhibitors; Receptors, Cytoplasmic and Nuclear; Ryanodine; Second Messenger Systems; Thionucleotides