the tetrodotoxin receptor of voltage-gated sodium channels—perspectives from interactions with μ-conotoxins电压门控钠channels-perspectives的河豚毒素受体与μ-conotoxins的交互.pdfVIP

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the tetrodotoxin receptor of voltage-gated sodium channels—perspectives from interactions with μ-conotoxins电压门控钠channels-perspectives的河豚毒素受体与μ-conotoxins的交互.pdf

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the tetrodotoxin receptor of voltage-gated sodium channels—perspectives from interactions with μ-conotoxins电压门控钠channels-perspectives的河豚毒素受体与μ-conotoxins的交互

Mar. Drugs 2010, 8, 2153-2161; doi:10.3390/md8072153 OPEN ACCESS Marine Drugs ISSN 1660-3397 /journal/marinedrugs Review The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins Robert J. French 1,*, Doju Yoshikami 2, Michael F. Sheets 3 and Baldomero M. Olivera 2 1 Department of Physiology and Pharmacology, University of Calgary, and Hotchkiss Brain Institute, 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1, Canada 2 Department of Biology; University of Utah; Salt Lake City, UT, USA; E-Mails: yoshikami@ (D.Y.); olivera@ (B.M.O.) 3 The Nora Eccles Harrison Cardiovascular Research Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA; E-Mail: sheets@ * Author to whom correspondence should be addressed; E-Mail: french@ucalgary.ca; Tel.: +1-403-220-6893; Fax: +1-403-210-7446. Received: 2 June 2010; in revised form: 24 June 2010 / Accepted: 25 June 2010 / Published: 13 July 2010 Abstract : Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins