The voltage-gated sodium channel generates the action potential. This 300-kDa protein has four homologous regions, which are also homologous to the voltage-sensitive tetrameric potassium channel. We isolated sodium channels from Electrophorus electricus electroplax by detergent solubilization and immunoaffinity chromatography and studied their structure by electron microscopy of negatively stained specimens. Different projections were aligned, classified, and averaged. In side view, the channel protein exhibits the shape of a truncated cone, 14 nm in height. One end has a diameter of 12 nm and is asymmetric, while the other is more symmetric and has a diameter of 7-10 nm. In top views, the sodium channel appears to consist of four domains of different size and to have a stain-filled pore in the center.