Mutant SOD1 forms ion channel: Implications for ALS pathophysiology

► Compelling new evidence for toxic channel mechanism of cell injury in ALS. ► A4V mutant was studied using complementary techniques. ► High resolution AFM revealed tetrameric pore structures in lipid bilayers. ► Heterogeneous single channel conductance was observed in lipid bilayers. ► Plasma membrane depolarization and cell calcium loading were observed in N2A cells.