How does the membrane electric field gate an ion channel open and close?

Francisco Bezanilla, Departments of Physiology and Anesthesiology. University of California at Los Angeles, Los Angeles, CA, U.S.A. Voltage dependent sodium and potassium channels are responsible for the generation and propagation of the nerve impulse. Voltage dependence is achieved by the translocation of about 12 e across the membrane field. The movement of this charge generates a transient current called gating current that precedes channel opening. Most of the gating charge is located in the first most extracellular arginines of the fourth transmembrane helix (S4 segment) found in voltage-gated channels. Accessibility studies with protons in mutants that replace the arginines by histidine, reveal that those residues are alternatively exposed to the inside at hyperpolarized potentials and outside at depolarized potentials because the histidine-replaced voltage sensor can act as a proton transporter. The most extracellular site generates a proton pore in the closed state, ...  more