Glutamate regulates IP3-type and CICR stores in the avian cochlear nucleus

Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are ac tivated by glutamate released from auditory nerve terminals. If this stimul ation is removed, the intracellular calcium ion concentration ([Ca2+](i)) o f NM neurons rises and rapid atrophic changes ensue. We have been investiga ting mechanisms that regulate [Ca2+](i) in these neurons based on the hypot hesis that loss of Ca2+ homeostasis causes the cascade of cellular changes that results in neuronal atrophy and death. In the present study, video-enh anced fluorometry was used to monitor changes in [Ca2+](i) stimulated by ag ents that mobilize Ca2+ from intracellular stores and to study the modulati on of these responses by glutamate. Homobromoibotenic acid (HBI) was used t o stimulate inositol trisphosphate (IP3)-sensitive stores, and caffeine was used to mobilize Ca2+ from Ca2+-induced Ca2+ release (CICR) stores. We pro vide data indicating that Ca2+ responses attributable to IF3- and CICR-sens itive stores are inhibited by glutamate, acting via a metabotropic glutamat e receptor (mGluR). We also show that activation of C-kinase by a phorbol e ster will reduce HBI-stimulated calcium responses. Although the protein kin ase A accumulator, Sp-cAMPs, did not have an effect on HBI-induced response s. CICR-stimulated responses were not consistently attenuated by either the phorbol eater or the Sp-cAMPs. We have previously shown that glutamate att enuates voltage-dependent changes in [Ca2+](i). Coupled with the present fi ndings, this suggests that in these neurons mGluRs serve to limit fluctuati ons in intracellular Ca2+ rather than increase [Ca2+](i). This system may p lay a role in protecting highly active neurons from calcium toxicity result ing in apoptosis.