Glutamatergic inhibition of voltage-operated calcium channels in the avian cochlear nucleus.
The auditory nerve serves as the only excitatory input to neurons in the avian cochlear nucleus, nucleus magnocellularis (NM). NM neurons in immature animals are dependent upon auditory nerve signals; when deprived of them, many NM neurons die, and the rest atrophy. Auditory nerve terminals release glutamate, which can stimulate second messenger systems by activating a metabotropic glutamate receptor (mGluR). Therefore, it is possible that the effectors of mGluR-stimulated signal transduction systems are needed for NM neuronal survival. This study shows that mGluR activation in NM neurons attenuates voltage-dependent changes in [Ca2+]j. Voltage-dependent Ca2+ influx was also attenuated by increasing cAMP with forskolin, VIP, or 8-bromo-cAMP, indicating that mGluR activation may stimulate adenylate cyclase. The main results may be summarized as follows. NM neurons possess high voltage-activated Ca2+ channels that were modulated by quisqualate, glutamate, and (+/-)trans-ACPD, in that order of potency. Glutamatergic inhibition of Ca2+ influx was not blocked by L-AP3 or L-AP4, which antagonize the actions of mGluRs in other neural systems; it was blocked by serine-O-phosphate. Finally, the attenuation of voltage-dependent Ca2+ influx was duplicated by cAMP accumulators. Since NM neurons have high rates of spontaneous activity and higher rates of driven activity, the expression of this mGluR turns out to be very valuable: without it, [Ca2+]j could reach lethal concentrations. These results provide an important clue as to the identity of an intracellular signal that may play an important role in NM neuronal survival.
Lachica
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EA
Department of Otolaryngology-Head and Neck Surgery, Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle 98195.
Rübsamen
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R
Zirpel
L
L
Rubel
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EW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002642:Chick Embryo; D017626:Cochlear Nucleus / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism; D017470:Receptors, Glutamate / Q000502:physiology*; D015398:Signal Transduction
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D000242:Cyclic AMP; D002118:Calcium