Depolarization exposes the voltage sensor of the sodium channels to the extracellular region.

Two domains of Na channels were mapped with site-specific antibodies raised in rabbit against synthetic peptides corresponding to a part of the voltage sensor of internal repeat 1-C1+ (amino acids 210-223) and to a region designated dipole (amino acids 1690-1699) of eel electroplax sodium channels. The antibodies bind to their respective domains in both purified and membrane-bound channels and immunoprecipitate the channels from eel electroplax and rat brain synaptosomes. Anti-C1+ depresses the action potential of rat sciatic nerve in a concentration-dependent way. It binds to the external side of rat brain synaptosomal vesicle, and its binding is potentiated by depolarization. Anti-dipole binds to the inner side of the vesicle, and the binding is inhibited by depolarization.