Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET

• DOI: 10.1073/pnas.1700453114
• Publication Date: 2017-02-16T02:10:46Z
• Authors: Tomoya Kubota; Thomas Durek; Bobo Dang; Rocio K. Finol-Ur...; David J. Craik; Stephen B. H. Kent; Robert J. French; Francisco Bezanilla; Ana M. Correa
• Keywords: Boron Compounds; 571; Patch-Clamp Techniques; Slow inactivation; 1.1 Normal biological development and functioning; Xenopus; Muscle Proteins; Scorpion Venoms; μ-conotoxin; Voltage-Gated Sodium Channels; relaxed state; Relaxed state; Lanthanoid Series Elements; Sodium Channels; Membrane Potentials; 03 medical and health sciences; Underpinning research; beta-scorpion toxin; Medicine and Health Sciences; Animals; Muscle, Skeletal; slow inactivation; 0303 health sciences; Binding Sites; Neurosciences; voltage gating; Skeletal; Rats; Kinetics; Voltage gating; Energy Transfer; 1000 General; mu-conotoxin; Oocytes; Muscle; β-scorpion toxin

Significance Physical activities of our body and extremities are achieved by the propagation of electrical signals called action potentials from our brain, through nerves, to skeletal muscles. Voltage-gated sodium channel (Navs) play essential roles in the generation and propagation of action potentials in such excitable cells. Although mammalian Nav function has been studied comprehensively, the precise structural basis for the gating mechanisms has not been fully clarified. In this study, we have used lanthanide-based resonance energy transfer to obtain dynamic structural information in mammalian Nav gating. Our data define a geometrical map of Navs with the bound toxins and reveal voltage-induced structural changes related to channel gating, which lead us further toward an understanding of the gating mechanism in mammalian Navs.