2905921

Glutamate cytotoxicity in a neuronal cell line is blocked by membrane depolarization.

Article date: 1988/9/13

PubMed ID: 2905921

Journal name: Brain research (ISSN: 0006-8993)

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.

Author List: Murphy T H, Schnaar R L, Coyle J T, Sastre A

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Glutamates; Neurotoxins; Oxadiazoles; Ibotenic Acid; Glutamic Acid; Quisqualic Acid;

Mesh terms: Animals; Cell Line; Glutamates/pharmacology; Glutamic Acid; Hybrid Cells/physiology; Ibotenic Acid/pharmacology; Membrane Potentials/drug effects; Neuroblastoma; Neurons/drug effects; Neurotoxins; Oxadiazoles/pharmacology; Quisqualic Acid; Retina;

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