Voltage-activated sodium currents in a cell line expressing a Cu,Zn superoxide dismutase typical of familial ALS

The whole-cell configuration of the patch-clamp recording was used to study the voltage-dependent Na⁺ currents in a model system for the familial form of amyotrophic lateral sclerosis (ALS) associated with mutations in Cu,Zn superoxide dismutase. Here we report that the amplitude of voltage- gated Na⁺ currents is significantly reduced in cell lines expressing mutant Cu,Zn superoxide dismutase G93A when compared with the parental, untransfected cell line and to a cell line expressing the wild-type enzyme. This effect is associated with a shift toward positive values of the steady- state inactivation curve of the Na⁺ currents. These results indicate that expression of a Cu,Zn superoxide dismutase typical of patients affect with familial ALS influence the functionality of the voltage-dependent Na⁺ channels; this effect may contribute to the pathogenesis of the disease.