The Journal of Neurophysiology Vol. 81 No. 4 April 1999, pp. 1587-1596
Copyright ©1999 by the American Physiological Society

Glutamate Regulates IP₃-Type and CICR Stores in the Avian Cochlear Nucleus

Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, Washington 98195

Kato, B. Maya and Edwin W Rubel. Glutamate regulates IP₃-type and CICR stores in the avian cochlear nucleus. 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.