Molecular Basis of Charge Movement in Voltage-Gated Sodium Channels

• Published in: Neuron (Cambridge, Mass.) Vol. 16; no. 1; pp. 113 - 122
• Main Authors: Yang, Naibo, George, Alfred L, Horn, Richard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1996
• Subjects: Amino Acid Sequence; Base Sequence; Cell Line; Chemical Phenomena; Chemistry, Physical; Cysteine - chemistry; Humans; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Mammalia; Membrane Potentials - drug effects; Models, Molecular; Molecular Sequence Data; Muscle, Skeletal - chemistry; Mutagenesis, Site-Directed; Protein Conformation; Recombinant Fusion Proteins - chemistry; Sodium - physiology; Sodium Channels - chemistry; Sodium Channels - drug effects; Sodium Channels - genetics; Sodium Channels - physiology; Sulfhydryl Reagents - pharmacology; Transfection
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80028-8

Voltage-dependent movement of a sodium channel S4 segment was examined by cysteine scanning mutagenesis and testing accessibility of the residues to hydrophilic cysteine-modifying reagents. These experiments indicate that 2 charged S4 residues move completely from an internally accessible to an externally accessible location in response to depolarization by passage through a short “channel” in the protein. The energetic problems of S4 movement have thus been solved in the same way that many ion channels achieve highly selective and rapid ion permeation through an open pore, by restricting the contact region between the permion and its channel.