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

T. H. Murphy, R. L. Schnaar, J. T. Coyle, A. Sastre

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)155-160
Number of pages6
JournalBrain research
Volume460
Issue number1
DOIs
StatePublished - Sep 13 1988

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Keywords

  • Calcium
  • Cell culture
  • Depolarization
  • Glutamate
  • Neuroblastoma
  • Neurotoxicity
  • Quisqualate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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