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 s uperoxide dismutase G93A when compared with the parental, untransfected cel l line and to a cell line expressing the wild-type enzyme. This effect is a ssociated with a shift toward positive values of the steady-state inactivat ion curve of the Na+ currents. These results indicate that expression of a Cu,Zn superoxide dismutase typical of patients affect with familial ALS inf luence the functionality of the voltage-dependent Na+ channels; this effect may contribute to the pathogenesis of the disease. (C) 1998 Lippincott Wil liams & Wilkins.