Extracellular Acidosis, Cysteine, and Glutathione Enhance the Toxic Effect of Copper Ions in Cultures of Cerebellar Granule Neurons.

We studied the effect of extracellular acidosis, cysteine, glutathione, and iron ions (Fe³⁺) on the neurocytotoxic effect of copper ions (Cu²⁺) in vitro. At acidic pH of the culture medium (pH 6.8), the toxic effect of copper on cultured neurons significantly increased in comparison with that at neutral pH 7.3. In the presence of 25 μM Cu²⁺ in the culture medium at pH 7.3 and 6.8, the neuronal survival was 89±2 and 63±4%, respectively. In the presence of glutathione or cysteine (1 μM) in the culture medium, even 0.5 μM Cu²⁺ caused 100% death of cultured neurons, while the presence of Fe³⁺ (10-50 μM) had no effect on the toxicity of Cu²⁺. In general, acidosis or the presence of glutathione or cysteine increases the cytotoxicity of copper ions.