title: Voltage-gated sodium channels viewed through a structural biology lens.
abstract: Voltage-gated sodium (Nav) channels initiate and propagate action potentials in excitable cells, and are frequently dysregulated or mutated in human disease. Despite decades of intense physiological and biophysical research, eukaryotic Nav channels have so far eluded high-resolution structure determination because of their biochemical complexity. Recently, simpler bacterial voltage-gated sodium (BacNav) channels have provided templates to understand the structural basis of voltage-dependent activation, inactivation, ion selectivity, and drug block in eukaryotic Nav and related voltage-gated calcium (Cav) channels. Further breakthroughs employing BacNav channels have also enabled visualization of bound small molecule modulators that can guide the rational design of next generation therapeutics. This review will highlight the emerging structural biology of BacNav channels and its contribution to our understanding of the gating, ion selectivity, and pharmacological regulation of eukaryotic Nav (and Cav) channels.
authors.affiliation: Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clairfeuille
authors.affiliation: Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Koth
authors.affiliation: Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. Electronic address: payandeh.jian@gene.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Payandeh
mesh_terms: D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D016062:Porosity; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D061566:Voltage-Gated Sodium Channels