Excitatory Amino Acid‐Induced Toxicity in Chick Retina: Amino Acid Release, Histology, and Effects of Chloride Channel Blockers

Gail D. Zeevalk, Arnold Hyndman, William J. Nicklas

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79 Scopus citations


Abstract: Acute excitotoxicity in embryonic chick retina and the ability of C1 channel blockers to prevent toxicity were evaluated by measurement of endogenous amino acid release and histology. Treatment of retina with kainate, quisqualate, or N‐methyl‐D‐aspartate resulted in a large dose‐dependent release of γ‐aminobutyric acid and taurine, moderate release of glutamine and alanine, and no measurable release of glu‐tamate or aspartate. Concentrations inducing maximal γ‐aminobutyric acid release were 50 μM quisqualate, 100 μM kainate, and 100 μM N‐methyl‐D‐aspartate. Treatment with 1 mM glutamate resulted in significant γ‐aminobutyric acid release, as well as an elevation in medium aspartate levels. Typical excitotoxic retinal lesions were produced by the agonists and, at the lower concentrations tested, revealed a regional sensitivity. There was a positive correlation between the amount of γ‐aminobutyric acid release and the extent of tissue swelling, suggesting that release may be secondary to toxic cellular events. Omission of C1 completely blocked cytotoxic effects due to kainate or glutamate. Likewise, addition of the C1/bicarbonate anion channel blocker 4,4′‐di‐isothiocyanatostilbene‐2,2′‐disulfonate at 600 μM protected retina from cytotoxic damage from all excitotoxic analogs and restored amino acid levels to baseline values. Furosemide. which blocks Na+/K+/2C1 cotransport, was only minimally effective in reducing amino acid release induced by the agonists. Consistent with the latter, histological examination showed the continued presence of the lesion but with general reduction of cellular edema. These results indicate that although influx of C1 is a central component of the acute excitotoxic phenomenon, mechanisms other than passive Clflux may be involved.

Original languageEnglish (US)
Pages (from-to)1610-1619
Number of pages10
JournalJournal of neurochemistry
Issue number5
StatePublished - Nov 1989

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience


  • 4,4′‐Diisothiocyanatostilbene‐2,2′‐disulfonate
  • Amino acids
  • Excitotoxicity
  • Histology
  • Retina

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