RT Journal Article SR Electronic T1 Ca2+-Independent Excitotoxic Neurodegeneration in Isolated Retina, an Intact Neural Net: A Role for Cl and Inhibitory Transmitters JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 564 OP 572 DO 10.1124/mol.53.3.564 VO 53 IS 3 A1 Quan Chen A1 John W. Olney A1 Peter D. Lukasiewicz A1 Todd Almli A1 Carmelo Romano YR 1998 UL http://molpharm.aspetjournals.org/content/53/3/564.abstract AB Rapidly triggered excitotoxic cell death is widely thought to be due to excessive influx of extracellular Ca2+, primarily through the N-methyl-d-aspartate subtype of glutamate receptor. By devising conditions that permit the maintenance of isolated retina in the absence of Ca2+, it has become technically feasible to test the dependence of excitotoxic neurodegeneration in this intact neural system on extracellular Ca2+. Using biochemical, Ca2+ imaging, and electrophysiological techniques, we found that (1) rapidly triggered excitotoxic cell death in this system occurs independently of both extracellular Ca2+ and increases in intracellular Ca2+; (2) this cell death is highly dependent on extracellular Cl−; and (3) lethal Cl− entry occurs by multiple paths, but a significant fraction occurs through pathologically activated γ-aminobutyric acid and glycine receptors. These results emphasize the importance of Ca2+-independent mechanisms and the role that local transmitter circuitry plays in excitotoxic cell death.