Bacterial Voltage-Gated Sodium Channels (BacNaVs) from the Soil, Sea, and Salt Lakes Enlighten Molecular Mechanisms of Electrical Signaling and Pharmacology in the Brain and Heart. Issue 1 (16th January 2015)

• Record Type: Journal Article
• Authors: Payandeh, Jian; Minor, Daniel L.
• Is Part Of: Journal of molecular biology. Volume 427:Issue 1(2015:Jan. 01)
• Page Start: 3
• Page End: 30
• Publication Date: 2015-01-16
• Subjects: VGIC voltage-gated ion channel -- TRP transient receptor potential -- VSD voltage sensor domain -- PD pore-forming domain -- SF selectivity filter -- CTD C-terminal domain -- MD molecular dynamics -- HCS hydrophobic constriction site -- CTC charge transfer center -- VSP voltage-sensitive phosphatase; voltage-gated sodium channel -- structural biology -- channel gating -- ion permeation -- channel pharmacology; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2014.08.010
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Voltage-gated sodium channels (NaV s) provide the initial electrical signal that drives action potential generation in many excitable cells of the brain, heart, and nervous system. For more than 60 years, functional studies of NaV s have occupied a central place in physiological and biophysical investigation of the molecular basis of excitability. Recently, structural studies of members of a large family of bacterial voltage-gated sodium channels (BacNaV s) prevalent in soil, marine, and salt lake environments that bear many of the core features of eukaryotic NaV s have reframed ideas for voltage-gated channel function, ion selectivity, and pharmacology. Here, we analyze the recent advances, unanswered questions, and potential of BacNaV s as templates for drug development efforts. Graphical abstract: Highlights: Bacterial sodium channels (BacNaV s) offer unprecedented structural insights into voltage-gated ion channel function. BacNaV structures reveal the details of sodium and calcium-selective pores. BacNaV structures offer plausible models to understand the action of drugs.