Journal ArticleDOI
The Na(V)1.7 sodium channel: from molecule to man.
Sulayman D. Dib-Hajj,Yang Yang,Yang Yang,Joel A. Black,Joel A. Black,Stephen G. Waxman,Stephen G. Waxman +6 more
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TLDR
Homology modelling based on crystal structures of ion channels suggests an atomic-level structural basis for the altered gating of mutant NaV1.7 that causes pain.Abstract:
Mutations in SCN9A, which encodes the voltage-gated sodium channel NaV1.7, can lead to severe neuropathic pain in humans. In this Review, Waxman and colleagues examine the mechanistic basis of NaV1.7-linked pain and explore strategies for targeting this channel in pain therapy.read more
Citations
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Journal ArticleDOI
Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications
TL;DR: The current status of research in the Na( v) field is summarized and the most relevant recent developments with respect to the molecular structure, general physiology, and pharmacology of distinct Na(v) channel subtypes are presented.
Journal ArticleDOI
Regulating excitability of peripheral afferents: emerging ion channel targets.
TL;DR: An overview of recent advances on sodium, calcium, potassium and chloride channels that are emerging as especially attractive targets for the treatment of pain is given.
Journal ArticleDOI
The hitchhiker’s guide to the voltage-gated sodium channel galaxy
TL;DR: The current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins are synthesized in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts.
Journal ArticleDOI
Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist.
Shivani Ahuja,Susmith Mukund,Lunbin Deng,Kuldip Khakh,Elaine Chang,Hoangdung Ho,Stephanie Shriver,Clint Young,Sophia Lin,J. P. Johnson,Ping Wu,Jun Li,Mary Coons,Christine Tam,Bobby Brillantes,Honorio Sampang,Kyle Mortara,Krista K. Bowman,Kevin R Clark,Alberto Estevez,Zhiwei Xie,Henry Verschoof,Michael Edward Grimwood,Christoph Martin Dehnhardt,Jean-Christophe Andrez,Thilo Focken,Daniel P. Sutherlin,Brian Safina,Melissa A. Starovasnik,Daniel F. Ortwine,Yvonne Franke,Charles J. Cohen,David H. Hackos,Christopher M. Koth,Jian Payandeh +34 more
TL;DR: A novel protein-engineering strategy is devised that overcomes the technical complexities of producing full-length human Nav channels and demonstrates how this important new class of gating modifier engages VSD4 to inhibit Nav channel activity through a “voltage-sensor trapping” mechanism.
Journal ArticleDOI
A de novo gain-of-function mutation in SCN11A causes loss of pain perception
Enrico Leipold,Lutz Liebmann,G. Christoph Korenke,Theresa Heinrich,Sebastian Gießelmann,Jonathan Baets,Matthias Ebbinghaus,R. Oliver Goral,Tommy Stödberg,J. Christopher Hennings,Markus Bergmann,Janine Altmüller,Holger Thiele,Andrea Wetzel,Peter Nürnberg,Vincent Timmerman,Peter De Jonghe,Robert Blum,Hans-Georg Schaible,Joachim Weis,Stefan H. Heinemann,Christian A. Hübner,Ingo Kurth +22 more
TL;DR: Using exome sequencing, a specific de novo missense mutation in SCN11A is identified in individuals with the congenital inability to experience pain who suffer from recurrent tissue damage and severe mutilations, suggesting an alternative way to modulate pain perception.
References
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William A. Catterall,K. G. Chandy,David E. Clapham,George A. Gutman,Franz Hofmann,Anthony J. Harmar,Darrell R. Abernethy,Michael Spedding +7 more
TL;DR: This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined.
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