title: Glutamate cytotoxicity in a neuronal cell line is blocked by membrane depolarization.
abstract: To understand better the proximate mechanism involved in the excitotoxic response to L-glutamate (Glu), we have exploited the Glu receptor present in the N18-RE-105 neuroblastoma-embryonic retinal hybrid cell line. These cells undergo lysis dependent on extracellular Ca2+ when exposed to Glu. We now report that the depolarizing action of Glu is not responsible for its cytotoxic effects. Furthermore, depolarization of these cells with elevated K+, ouabain or veratridine does not cause cytotoxicity but rather protects against the cytotoxic effects of Glu. Our results may implicate a role for voltage-sensitive Ca2+ channels (VSCCs) in cytotoxicity, and depolarization-induced inactivation of VSCCs (Nature (Lond.), 316 (1985) 440-443) as a protection against Glu receptor agonists. Our findings demonstrate a clear dissociation between depolarization and the neuronal degeneration caused by Glu.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: T H
authors.initials: TH
authors.lastname: Murphy
authors.forename: R L
authors.initials: RL
authors.lastname: Schnaar
authors.forename: J T
authors.initials: JT
authors.lastname: Coyle
authors.forename: A
authors.initials: A
authors.lastname: Sastre
mesh_terms: D000818:Animals; D002460:Cell Line; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006822:Hybrid Cells / Q000502:physiology; D007051:Ibotenic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D012160:Retina
chemical_list: D005971:Glutamates; D009498:Neurotoxins; D010069:Oxadiazoles; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016318:Quisqualic Acid