Voltage-gated sodium channels viewed through a structural biology lens. (August 2017)

• Record Type: Journal Article
• Authors: Clairfeuille, Thomas; Xu, Hui; Koth, Christopher M; Payandeh, Jian
• Is Part Of: Current opinion in structural biology. Volume 45(2017)
• Page Start: 74
• Page End: 84
• Publication Date: 2017-08
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2016.11.022
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Bacterial voltage-gated sodium (BacNav) channels provide insight into eukaryotic Nav channel gating, ion selectivity and pharmacology. Highlights: BacNav channel structures reveal insights into gating, ion selectivity and drug block. Structures with bound modulators provide templates to design new therapeutics. Membrane lipids modify the function and pharmacology of voltage-gated ion channels. 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.