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      Overview of the voltage-gated sodium channel family

       1, 1

      Genome Biology

      BioMed Central

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          Abstract

          Different sodium channels have remarkably similar functional properties, but small changes in sodium-channel function are biologically relevant, as underscored by mutations that cause several human diseases of hyperexcitability.

          Abstract

          Selective permeation of sodium ions through voltage-dependent sodium channels is fundamental to the generation of action potentials in excitable cells such as neurons. These channels are large integral membrane proteins and are encoded by at least ten genes in mammals. The different sodium channels have remarkably similar functional properties, but small changes in sodium-channel function are biologically relevant, as underscored by mutations that cause several human diseases of hyperexcitability.

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          Most cited references 52

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          The structure of the potassium channel: molecular basis of K+ conduction and selectivity.

          The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective K+ conduction.
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            • Record: found
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            A quantitative description of membrane current and its application to conduction and excitation in nerve.

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              From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.

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                Author and article information

                Affiliations
                [1]Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA
                Correspondence: William A Catterall. E-mail: wcatt@u.washington.edu
                Contributors
                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London)
                1465-6906
                1465-6914
                2003
                24 February 2003
                : 4
                : 3
                : 207
                153452
                gb-2003-4-3-207
                12620097
                Copyright © 2003 BioMed Central Ltd
                Categories
                Review

                Genetics

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