title: Pharmacological insights and quirks of bacterial sodium channels.
abstract: The pedigree of voltage-gated sodium channels spans the millennia from eukaryotic members that initiate the action potential firing in excitable tissues to primordial ancestors that act as enviro-protective complexes in bacterial extremophiles. Eukaryotic sodium channels (eNavs) are central to electrical signaling throughout the cardiovascular and nervous systems in animals and are established clinical targets for the therapeutic management of epilepsy, cardiac arrhythmia, and painful syndromes as they are inhibited by local anesthetic compounds. Alternatively, bacterial voltage-gated sodium channels (bNavs) likely regulate the survival response against extreme pH conditions, electrophiles, and hypo-osmotic shock and may represent a founder of the voltage-gated cation channel family. Despite apparent differences between eNav and bNav channel physiology, gating, and gene structure, the discovery that bNavs are amenable to crystallographic study opens the door for the possibility of structure-guided rational design of the next generation of therapeutics that target eNavs. Here we summarize the gating behavior of these disparate channel members and discuss mechanisms of local anesthetic inhibition in light of the growing number of bNav structures.
authors.affiliation: Research School of Biology, The Australian National University, Canberra, ACT, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
authors.forename: Sora
authors.initials: S
authors.lastname: Lee
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ahern
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008958:Models, Molecular; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000779:Anesthetics, Local; D001426:Bacterial Proteins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium