PT  - JOURNAL ARTICLE
AU  - Quan Chen
AU  - John W. Olney
AU  - Peter D. Lukasiewicz
AU  - Todd Almli
AU  - Carmelo Romano
TI  - Ca<sup>2+</sup>-Independent Excitotoxic Neurodegeneration in Isolated Retina, an Intact Neural Net: A Role for Cl<sup>−</sup> and Inhibitory Transmitters
AID  - 10.1124/mol.53.3.564
DP  - 1998 Mar 01
TA  - Molecular Pharmacology
PG  - 564--572
VI  - 53
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/53/3/564.short
4100  - http://molpharm.aspetjournals.org/content/53/3/564.full
SO  - Mol Pharmacol1998 Mar 01; 53
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.