Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a
Identifieur interne : 000862 ( Pmc/Curation ); précédent : 000861; suivant : 000863Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a
Auteurs : Jennifer R. Deuis [Australie] ; Zoltan Dekan [Australie] ; Joshua S. Wingerd [Australie] ; Jennifer J. Smith [Australie] ; Nehan R. Munasinghe [Australie] ; Rebecca F. Bhola [Australie] ; Wendy L. Imlach [Australie] ; Volker Herzig [Australie] ; David A. Armstrong [Australie] ; K. Johan Rosengren [Australie] ; Frank Bosmans [États-Unis] ; Stephen G. Waxman [États-Unis] ; Sulayman D. Dib-Hajj [États-Unis] ; Pierre Escoubas [France] ; Michael S. Minett [Royaume-Uni] ; Macdonald J. Christie [Australie] ; Glenn F. King [Australie] ; Paul F. Alewood [Australie] ; Richard J. Lewis [Australie] ; John N. Wood [Royaume-Uni] ; Irina Vetter [Australie]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula
Url:
DOI: 10.1038/srep40883
PubMed: 28106092
PubMed Central: 5247677
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Deuis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dekan, Zoltan" sort="Dekan, Zoltan" uniqKey="Dekan Z" first="Zoltan" last="Dekan">Zoltan Dekan</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wingerd, Joshua S" sort="Wingerd, Joshua S" uniqKey="Wingerd J" first="Joshua S." last="Wingerd">Joshua S. 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Smith</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Munasinghe, Nehan R" sort="Munasinghe, Nehan R" uniqKey="Munasinghe N" first="Nehan R." last="Munasinghe">Nehan R. Munasinghe</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bhola, Rebecca F" sort="Bhola, Rebecca F" uniqKey="Bhola R" first="Rebecca F." last="Bhola">Rebecca F. Bhola</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Imlach, Wendy L" sort="Imlach, Wendy L" uniqKey="Imlach W" first="Wendy L." last="Imlach">Wendy L. Imlach</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Herzig, Volker" sort="Herzig, Volker" uniqKey="Herzig V" first="Volker" last="Herzig">Volker Herzig</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Armstrong, David A" sort="Armstrong, David A" uniqKey="Armstrong D" first="David A." last="Armstrong">David A. Armstrong</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>School of Biomedical Sciences, The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rosengren, K Johan" sort="Rosengren, K Johan" uniqKey="Rosengren K" first="K. Johan" last="Rosengren">K. Johan Rosengren</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>School of Biomedical Sciences, The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bosmans, Frank" sort="Bosmans, Frank" uniqKey="Bosmans F" first="Frank" last="Bosmans">Frank Bosmans</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Physiology & Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine</institution>, Baltimore, MD 21205,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Waxman, Stephen G" sort="Waxman, Stephen G" uniqKey="Waxman S" first="Stephen G." last="Waxman">Stephen G. Waxman</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System</institution>, West Haven, Connecticut 06516,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dib Hajj, Sulayman D" sort="Dib Hajj, Sulayman D" uniqKey="Dib Hajj S" first="Sulayman D." last="Dib-Hajj">Sulayman D. 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Minett</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Christie, Macdonald J" sort="Christie, Macdonald J" uniqKey="Christie M" first="Macdonald J." last="Christie">Macdonald J. Christie</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="King, Glenn F" sort="King, Glenn F" uniqKey="King G" first="Glenn F." last="King">Glenn F. King</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alewood, Paul F" sort="Alewood, Paul F" uniqKey="Alewood P" first="Paul F." last="Alewood">Paul F. Alewood</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Richard J" sort="Lewis, Richard J" uniqKey="Lewis R" first="Richard J." last="Lewis">Richard J. Lewis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wood, John N" sort="Wood, John N" uniqKey="Wood J" first="John N." last="Wood">John N. Wood</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a8"><institution>School of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall St, Woolloongabba</institution>, Queensland, 4102,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28106092</idno><idno type="pmc">5247677</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247677</idno><idno type="RBID">PMC:5247677</idno><idno type="doi">10.1038/srep40883</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000863</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000863</idno><idno type="wicri:Area/Pmc/Curation">000862</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000862</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pharmacological characterisation of the highly Na<sub>V</sub>1.7 selective spider venom peptide Pn3a</title><author><name sortKey="Deuis, Jennifer R" sort="Deuis, Jennifer R" uniqKey="Deuis J" first="Jennifer R." last="Deuis">Jennifer R. Deuis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dekan, Zoltan" sort="Dekan, Zoltan" uniqKey="Dekan Z" first="Zoltan" last="Dekan">Zoltan Dekan</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wingerd, Joshua S" sort="Wingerd, Joshua S" uniqKey="Wingerd J" first="Joshua S." last="Wingerd">Joshua S. Wingerd</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith, Jennifer J" sort="Smith, Jennifer J" uniqKey="Smith J" first="Jennifer J." last="Smith">Jennifer J. Smith</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Munasinghe, Nehan R" sort="Munasinghe, Nehan R" uniqKey="Munasinghe N" first="Nehan R." last="Munasinghe">Nehan R. Munasinghe</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bhola, Rebecca F" sort="Bhola, Rebecca F" uniqKey="Bhola R" first="Rebecca F." last="Bhola">Rebecca F. Bhola</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Imlach, Wendy L" sort="Imlach, Wendy L" uniqKey="Imlach W" first="Wendy L." last="Imlach">Wendy L. Imlach</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Herzig, Volker" sort="Herzig, Volker" uniqKey="Herzig V" first="Volker" last="Herzig">Volker Herzig</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Armstrong, David A" sort="Armstrong, David A" uniqKey="Armstrong D" first="David A." last="Armstrong">David A. Armstrong</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>School of Biomedical Sciences, The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rosengren, K Johan" sort="Rosengren, K Johan" uniqKey="Rosengren K" first="K. Johan" last="Rosengren">K. Johan Rosengren</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>School of Biomedical Sciences, The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bosmans, Frank" sort="Bosmans, Frank" uniqKey="Bosmans F" first="Frank" last="Bosmans">Frank Bosmans</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Physiology & Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine</institution>, Baltimore, MD 21205,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Waxman, Stephen G" sort="Waxman, Stephen G" uniqKey="Waxman S" first="Stephen G." last="Waxman">Stephen G. Waxman</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System</institution>, West Haven, Connecticut 06516,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dib Hajj, Sulayman D" sort="Dib Hajj, Sulayman D" uniqKey="Dib Hajj S" first="Sulayman D." last="Dib-Hajj">Sulayman D. Dib-Hajj</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System</institution>, West Haven, Connecticut 06516,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Escoubas, Pierre" sort="Escoubas, Pierre" uniqKey="Escoubas P" first="Pierre" last="Escoubas">Pierre Escoubas</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Venomtech, Sophie-Antipolis</institution>, 06560, Valbonne,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Minett, Michael S" sort="Minett, Michael S" uniqKey="Minett M" first="Michael S." last="Minett">Michael S. Minett</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Christie, Macdonald J" sort="Christie, Macdonald J" uniqKey="Christie M" first="Macdonald J." last="Christie">Macdonald J. Christie</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="King, Glenn F" sort="King, Glenn F" uniqKey="King G" first="Glenn F." last="King">Glenn F. King</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alewood, Paul F" sort="Alewood, Paul F" uniqKey="Alewood P" first="Paul F." last="Alewood">Paul F. Alewood</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Richard J" sort="Lewis, Richard J" uniqKey="Lewis R" first="Richard J." last="Lewis">Richard J. Lewis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wood, John N" sort="Wood, John N" uniqKey="Wood J" first="John N." last="Wood">John N. Wood</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a8"><institution>School of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall St, Woolloongabba</institution>, Queensland, 4102,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human genetic studies have implicated the voltage-gated sodium channel Na<sub>V</sub>1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula <italic>Pamphobeteus nigricolor,</italic> potently inhibits Na<sub>V</sub>1.7 (IC<sub>50</sub> 0.9 nM) with at least 40–1000-fold selectivity over all other Na<sub>V</sub> subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na<sub>V</sub>1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na<sub>V</sub>1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na<sub>V</sub>1.7 inhibitors produced profound analgesia. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28106092</article-id><article-id pub-id-type="pmc">5247677</article-id><article-id pub-id-type="pii">srep40883</article-id><article-id pub-id-type="doi">10.1038/srep40883</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Pharmacological characterisation of the highly Na<sub>V</sub>1.7 selective spider venom peptide Pn3a</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Deuis</surname><given-names>Jennifer R.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dekan</surname><given-names>Zoltan</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wingerd</surname><given-names>Joshua S.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Jennifer J.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Munasinghe</surname><given-names>Nehan R.</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bhola</surname><given-names>Rebecca F.</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Imlach</surname><given-names>Wendy L.</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Herzig</surname><given-names>Volker</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Armstrong</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rosengren</surname><given-names>K. Johan</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bosmans</surname><given-names>Frank</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Waxman</surname><given-names>Stephen G.</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Dib-Hajj</surname><given-names>Sulayman D.</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Escoubas</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="a6">6</xref></contrib><contrib contrib-type="author"><name><surname>Minett</surname><given-names>Michael S.</given-names></name><xref ref-type="aff" rid="a7">7</xref></contrib><contrib contrib-type="author"><name><surname>Christie</surname><given-names>Macdonald J.</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>King</surname><given-names>Glenn F.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Alewood</surname><given-names>Paul F.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lewis</surname><given-names>Richard J.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wood</surname><given-names>John N.</given-names></name><xref ref-type="aff" rid="a7">7</xref></contrib><contrib contrib-type="author"><name><surname>Vetter</surname><given-names>Irina</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a8">8</xref></contrib><aff id="a1"><label>1</label><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></aff><aff id="a2"><label>2</label><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></aff><aff id="a3"><label>3</label><institution>School of Biomedical Sciences, The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></aff><aff id="a4"><label>4</label><institution>Department of Physiology & Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine</institution>, Baltimore, MD 21205,<country>USA</country></aff><aff id="a5"><label>5</label><institution>Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System</institution>, West Haven, Connecticut 06516,<country>USA</country></aff><aff id="a6"><label>6</label><institution>Venomtech, Sophie-Antipolis</institution>, 06560, Valbonne,<country>France</country></aff><aff id="a7"><label>7</label><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></aff><aff id="a8"><label>8</label><institution>School of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall St, Woolloongabba</institution>, Queensland, 4102,<country>Australia</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>i.vetter@uq.edu.au</email></corresp></author-notes><pub-date pub-type="epub"><day>20</day><month>01</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>7</volume><elocation-id>40883</elocation-id><history><date date-type="received"><day>29</day><month>09</month><year>2016</year></date><date date-type="accepted"><day>12</day><month>12</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2017, The Author(s)</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Human genetic studies have implicated the voltage-gated sodium channel Na<sub>V</sub>1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula <italic>Pamphobeteus nigricolor,</italic> potently inhibits Na<sub>V</sub>1.7 (IC<sub>50</sub> 0.9 nM) with at least 40–1000-fold selectivity over all other Na<sub>V</sub> subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na<sub>V</sub>1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na<sub>V</sub>1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na<sub>V</sub>1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na<sub>V</sub>1.7 inhibitors can only produce analgesia when administered in combination with an opioid.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>Isolation of the novel spider peptide μ-TRTX-Pn3a from the venom of <italic>Pamphobeteus nigricolor.</italic></title><p>(<bold>a</bold>) Photo of the male <italic>Pamphobeteus nigricolor</italic> specimen from which crude venom was obtained. (<bold>b</bold>) Chromatogram resulting from fractionation of the crude venom using RP-HPLC (purple dashed line indicates acetonitrile gradient). Corresponding activity of each fraction to inhibit veratridine-induced Na<sub>V</sub>1.3 responses is shown above (black circles). The arrow indicates the active peak. (<bold>c</bold>) Sequences of μ-TRTX-Pn3a and μ-TRTX-Pn3b identified by N-terminal sequencing.</p></caption><graphic xlink:href="srep40883-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Selectivity of μ-TRTX-Pn3a for hNa<sub>V</sub>1.1-1.9 channels.</title><p>(<bold>a</bold>) Concentration-response curves and (<bold>b</bold>) comparative potency of Pn3a at hNa<sub>V</sub>1.1-1.9 assessed by whole-cell patch-clamp experiments. Pn3a most potently inhibited Na<sub>V</sub>1.7, with 40-fold selectivity over hNa<sub>V</sub>1.1, 100-fold selectivity over hNa<sub>V</sub>1.2, 1.3, 1.4 and 1.6, and 900-fold selectivity over Na<sub>V</sub>1.5, Na<sub>V</sub>1.8, and Na<sub>V</sub>1.9. Data are presented as mean ± SEM, with n = 3–9 cells per data point. (<bold>c</bold>) Representative hNa<sub>V</sub>1.1-1.9 current traces before (black) and after addition of Pn3a (red). Currents were obtained by a 20 ms pulse of −20 mV for Na<sub>V</sub>1.1-1.7, a 20 ms pulse +10 mV for Na<sub>V</sub>1.8, and a 40 ms pulse of −40 mV for Na<sub>V</sub>1.9. Pn3a (10 nM) selectively inhibited peak current at hNa<sub>V</sub>1.7 only.</p></caption><graphic xlink:href="srep40883-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>Effect of μ-TRTX-Pn3a on the electrophysiological parameters of hNa<sub>V</sub>1.1-1.8.</title><p>I-V curves before (black triangles) and after addition of Pn3a (white triangles). Pn3a (100 nM) inhibited peak current at all Na<sub>V</sub> subtypes but caused a rightward shift in the I-V curve at Na<sub>V</sub>1.7 only. G-V curves before (black circles) and after addition of Pn3a (white circles). Pn3a (100 nM) significantly shifted the V<sub>1/2</sub> of voltage-dependence of activation to a more depolarized potential at Na<sub>V</sub>1.7 only (Δ + 21.3 mV). Voltage-dependence of steady-state fast inactivation curves before (black squares) and after addition of Pn3a (white squares). Pn3a (100 nM) caused small but significant shifts in the V<sub>1/2</sub> of steady-state fast inactivation at Na<sub>V</sub>1.1, 1.2, 1.3, 1.4, 1.7 and 1.8. Data are presented as mean ± SEM, with n = 4–10 cells per data point.</p></caption><graphic xlink:href="srep40883-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><title>Additional effects of μ-TRTX-Pn3a on the electrophysiological parameters of hNa<sub>V</sub>1.7.</title><p>(<bold>a</bold>) Time course of peak current reduction upon application of (arrow) 100 nM, 30 nM or 10 nM Pn3a at Na<sub>V</sub>1.7. Onset of block was measured with repetitive pulses to –20 mV every 20 s. Data are fitted with single-exponential functions and the time constant of block (τ) is indicated for each concentration. (<bold>b</bold>) Voltage-dependence of time-to-peak as a measure of activation kinetics at Na<sub>V</sub>1.7. Pn3a (100 nM) delayed time to peak between −20 mV and 15 mV. (<bold>c</bold>) Voltage-dependence of fast inactivation time constants at Na<sub>V</sub>1.7. Pn3a (100 nM) slowed the inactivation rate between −10 mV and 0 mV. (<bold>d</bold>) Rate of recovery from inactivation at Na<sub>V</sub>1.7. Pn3a (100 nM) slowed the rate of recovery from inactivation. Data are fitted with single-exponential functions and the time constant of recovery (τ) is indicated. (<bold>e</bold>) Steady-state slow inactivation at Na<sub>V</sub>1.7. Pn3a (100 nM) had no significant effect on the voltage-dependence of steady-state slow inactivation. Data are presented as mean ± SEM, with n = 4–6 cells per data point. Statistical significance was determined using two-way ANOVA, *<italic>P</italic> < 0.05 compared to control. (<bold>f</bold>) Representative ramp current elicited by a 50 ms depolarization from −100 to +20 mV at a rate of 2.4 mV/ms at Na<sub>V</sub>1.7. Pn3a (100 nM) inhibited ramp currents. (<bold>g</bold>) Potassium currents before (black) and in the presence of Pn3a (coloured) elicited by depolarisations to 70 mV in hNa<sub>v</sub>1.7/rK<sub>v</sub>2.1 chimeras. Pn3a (300 nM) inhibited potassium currents in the DII hNa<sub>V</sub>1.7/K<sub>V</sub>2.1 and DIV hNa<sub>V</sub>1.7/K<sub>V</sub>2.1 chimeras. Scale bars: 50 ms (abscissa), 2 μA (DI, DII, DIV, K<sub>V</sub>2.1) and 1 μA (DIII) (ordinate axis).</p></caption><graphic xlink:href="srep40883-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><title>Solution structure of Pn3a.</title><p>(<bold>a</bold>) The family of the 20 lowest energy structures superimposed over the backbone with disulfide bonds shown in yellow (Protein Data Bank code 5T4R). (<bold>b</bold>) The lowest energy structure with β-strands shown as arrows and disulfide bonds in ball and stick representation.</p></caption><graphic xlink:href="srep40883-f5"></graphic></fig><fig id="f6"><label>Figure 6</label><caption><title>Pn3a inhibits TTX-sensitive current in small-diameter DRG neurons and eEPSC in C-fibres from lamina I neurons.</title><p>(<bold>a</bold>) Percentage inhibition of sodium current by TTX and Pn3a in IB<sub>4</sub><sup>−</sup>, lightly IB<sub>4</sub><sup>+</sup> and strongly IB<sub>4</sub><sup>+</sup> small-diameter and large-diameter DRG neurons (n = 6–15). (<bold>b</bold>) Representative peak current vs time plot before and after addition of TTX and Pn3a in a small-diameter DRG neuron. (<bold>c</bold>) Representative peak current vs time plot before and after addition of TTX and Pn3a in a large-diameter DRG neuron (<bold>d</bold>) Representative current traces from a lamina I neuron indicating the position of the dorsal root evoked Aβ-, Aδ- and C-fibre currents pre- and post-treatment with Pn3a. (<bold>e</bold>) eEPSC amplitudes normalized to the baseline control for C-, Aδ-, Aβ-fibre currents in lamina I neurons treated with Pn3a (n = 7, 7 and 4, respectively). Data are presented as mean ± SEM. Statistical significance was determined using <italic>t</italic>-test compared to control, *<italic>P</italic> < 0.05.</p></caption><graphic xlink:href="srep40883-f6"></graphic></fig><fig id="f7"><label>Figure 7</label><caption><title>Analgesic effects of selective Na<sub>V</sub>1.7 inhibitors.</title><p>(<bold>a</bold>) Pn3a (i.p.) dose-dependently reversed spontaneous pain behaviours elicited by intraplantar injection of the Na<sub>V</sub>1.7 activator OD1 in mice (over 10 min); n = 3–9 per group. (<bold>b</bold>) Time course of reversal of OD1-induced spontaneous pain behaviours by Pn3a (3 mg/kg i.p.); n = 6 per group. (<bold>c</bold>) Effect of Pn3a (3 mg/kg i.p.) and PF-04856264 (30 mg/kg i.p.) on noxious heat assessed using the hotplate test (50 °C) in mice; n = 6–16 per group. Dashed line represents time spent on the hotplate by Na<sub>V</sub>1.7<sup>Wnt</sup> knockout mice. (<bold>d</bold>) Time course of effect of Pn3a (3 mg/kg i.p.) and (<bold>e</bold>) PF-04856264 (30 mg/kg i.p.) on formalin-induced spontaneous pain behaviours in mice; n = 4–15 per group. Effect of Pn3a (3 mg/kg i.p.) and PF-04856264 (30 mg/kg i.p.) on (<bold>f</bold>) carrageenan-induced mechanical allodynia and (<bold>g</bold>) carrageenan-induced thermal allodynia in mice; n = 4–12 per group. Effect of Pn3a (0.3 nmoles i.t.) on (<bold>h</bold>) FCA-induced mechanical allodynia, (<bold>i</bold>) FCA-induced thermal allodynia, and (<bold>j</bold>) motor performance on the Rotarod in rats; n = 4–9 per group. Data are presented as mean ± SEM. Statistical significance was determined using <italic>t</italic>-test, one-way or two-way ANOVA with Dunnett’s post-test as appropriate, *<italic>P</italic> < 0.05 compared to control.</p></caption><graphic xlink:href="srep40883-f7"></graphic></fig><fig id="f8"><label>Figure 8</label><caption><title>Selective Na<sub>V</sub>1.7 inhibitors synergize with opioids to produce analgesia.</title><p>(<bold>a</bold>) Time course of effect and (<bold>b</bold>) total pain behaviours with Pn3a (3 mg/kg i.p.), oxycodone (1 mg/kg i.p.) or the combination, in Phase I (0–10 min) and Phase II (10–55 min) of the formalin model in mice; n = 7–11 per group. Effect of Pn3a (3 mg/kg i.p.), PF-04856264 (30 mg/kg i.p.), oxycodone (0.66 mg/kg i.p.), or the combinations on (<bold>c</bold>) carrageenan-induced mechanical allodynia and (<bold>d</bold>) carrageenan-induced thermal allodynia in mice; n = 4–12 per group. (<bold>e</bold>) Effect of Phlotoxin-1 (50 μg/kg i.p.) and thiorphan (20 mg/kg i.p.) alone or in combination on acute heat responses; n = 6 per group (<bold>f</bold>) Effect of phlotoxin 1 (50 μg/kg i.p.) and buprenorphine (50 μg/kg i.p.) alone or in combination on acute heat responses; n = 6 per group. Effect of Pn3a (3 mg/kg i.p.) and gabapentin (100 mg/kg i.p.) alone or in combination on (<bold>g</bold>) carrageenan-induced mechanical allodynia and (<bold>h</bold>) carrageenan-induced thermal allodynia in mice; n = 3–8 per group. Data are presented as mean ± SEM. Statistical significance was determined using one-way or two-way ANOVA with Dunnett’s post-test as appropriate, *<italic>P</italic> < 0.05 compared to control.</p></caption><graphic xlink:href="srep40883-f8"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Potency of Pn3a at multiple ion channels.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50">Channel</th><th align="center" valign="top" charoff="50">IC<sub>50</sub> (nM)</th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.1</td><td align="center" valign="top" charoff="50">37</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.2</td><td align="center" valign="top" charoff="50">124</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.3</td><td align="center" valign="top" charoff="50">210</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.4</td><td align="center" valign="top" charoff="50">144</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.5</td><td align="center" valign="top" charoff="50">800</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.6</td><td align="center" valign="top" charoff="50">129</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.7</td><td align="center" valign="top" charoff="50">0.9</td></tr><tr><td align="left" valign="top" charoff="50">rNa<sub>V</sub>1.7</td><td align="center" valign="top" charoff="50">1.5</td></tr><tr><td align="left" valign="top" charoff="50">mNa<sub>V</sub>1.7</td><td align="center" valign="top" charoff="50">4.4</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.8</td><td align="center" valign="top" charoff="50">49888</td></tr><tr><td align="left" valign="top" charoff="50">hNa<sub>V</sub>1.9</td><td align="center" valign="top" charoff="50">2427</td></tr><tr><td align="left" valign="top" charoff="50">rK<sub>V</sub>2.1</td><td align="center" valign="top" charoff="50">>300</td></tr><tr><td align="left" valign="top" charoff="50">hCa<sub>V</sub>1.2</td><td align="center" valign="top" charoff="50">>10000</td></tr><tr><td align="left" valign="top" charoff="50">hCa<sub>V</sub>2.2</td><td align="center" valign="top" charoff="50">>10000</td></tr><tr><td align="left" valign="top" charoff="50">α7 nAChR</td><td align="center" valign="top" charoff="50">>10000</td></tr><tr><td align="left" valign="top" charoff="50">α3 nAChR</td><td align="center" valign="top" charoff="50">>10000</td></tr></tbody></table></table-wrap><table-wrap position="float" id="t2"><label>Table 2</label><caption><title>Effects of Pn3a (100 nM) on Na<sub>V</sub> channel voltage dependence of activation and steady-state fast inactivation.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th rowspan="2" align="center" valign="top" charoff="50"> </th><th rowspan="2" align="center" valign="top" charoff="50">Pn3a</th><th colspan="2" align="center" valign="top" charoff="50">Activation<hr></hr></th><th colspan="2" align="center" valign="top" charoff="50">Inactivation<hr></hr></th></tr><tr><th align="center" valign="top" charoff="50">V<sub>1/2</sub> (mV)</th><th align="center" valign="top" charoff="50"><italic>k</italic> (mV)</th><th align="center" valign="top" charoff="50">V<sub>1/2</sub> (mV)</th><th align="center" valign="top" charoff="50"><italic>k</italic> (mV)</th></tr></thead><tbody valign="top"><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.1</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−22.9 ± 0.3</td><td align="center" valign="top" charoff="50">4.0 ± 0.3</td><td align="center" valign="top" charoff="50">−50.7 ± 0.5</td><td align="center" valign="top" charoff="50">−4.8 ± 0.5</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−21.1 ± 1.1</td><td align="center" valign="top" charoff="50">8.8 ± 1.0*</td><td align="center" valign="top" charoff="50">−57.8 ± 1.0*</td><td align="center" valign="top" charoff="50">−5.4 ± 0.9</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.2</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−18.8 ± 0.3</td><td align="center" valign="top" charoff="50">4.4 ± 0.2</td><td align="center" valign="top" charoff="50">−52.6 ± 0.6</td><td align="center" valign="top" charoff="50">−4.0 ± 0.5</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−19.8 ± 0.4</td><td align="center" valign="top" charoff="50">5.6 ± 0.4*</td><td align="center" valign="top" charoff="50">−55.2 ± 0.9*</td><td align="center" valign="top" charoff="50">−3.9 ± 0.6</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.3</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−26.0 ± 0.5</td><td align="center" valign="top" charoff="50">4.2 ± 0.4</td><td align="center" valign="top" charoff="50">−62.6 ± 0.6</td><td align="center" valign="top" charoff="50">−5.6 ± 0.5</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−26.2 ± 0.5</td><td align="center" valign="top" charoff="50">4.2 ± 0.4</td><td align="center" valign="top" charoff="50">−59.4 ± 1.2*</td><td align="center" valign="top" charoff="50">−7.9 ± 1.1</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.4</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−35.1 ± 0.5</td><td align="center" valign="top" charoff="50">2.4 ± 0.5</td><td align="center" valign="top" charoff="50">−64.7 ± 0.2</td><td align="center" valign="top" charoff="50">−4.4 ± 0.1</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−36.1 ± 0.7</td><td align="center" valign="top" charoff="50">2.4 ± 0.6</td><td align="center" valign="top" charoff="50">−62.3 ± 0.6*</td><td align="center" valign="top" charoff="50">−4.8 ± 0.5</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.5</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−29.3 ± 0.4</td><td align="center" valign="top" charoff="50">5.4 ± 0.3</td><td align="center" valign="top" charoff="50">−77.7 ± 0.7</td><td align="center" valign="top" charoff="50">−5.7 ± 0.6</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−29.1 ± 0.9</td><td align="center" valign="top" charoff="50">6.5 ± 0.8</td><td align="center" valign="top" charoff="50">−80.1 ± 0.9</td><td align="center" valign="top" charoff="50">−6.0 ± 0.8</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.6</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−23.4 ± 0.6</td><td align="center" valign="top" charoff="50">4.5 ± 0.5</td><td align="center" valign="top" charoff="50">−59.4 ± 1.0</td><td align="center" valign="top" charoff="50">−6.2 ± 0.9</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−22.6 ± 0.9</td><td align="center" valign="top" charoff="50">5.0 ± 0.7</td><td align="center" valign="top" charoff="50">−62.5 ± 1.5</td><td align="center" valign="top" charoff="50">−6.4 ± 1.3</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.7</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−25.1 ± 0.5</td><td align="center" valign="top" charoff="50">4.5 ± 0.4</td><td align="center" valign="top" charoff="50">−67.2 ± 0.7</td><td align="center" valign="top" charoff="50">−5.2 ± 0.6</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−3.8 ± 0.8*</td><td align="center" valign="top" charoff="50">6.0 ± 0.6</td><td align="center" valign="top" charoff="50">−69.9 ± 0.7*</td><td align="center" valign="top" charoff="50">−4.9 ± 0.7</td></tr><tr><td rowspan="2" align="left" valign="middle" charoff="50">Na<sub>V</sub>1.8</td><td align="center" valign="top" charoff="50">−</td><td align="center" valign="top" charoff="50">−4.4 ± 0.8</td><td align="center" valign="top" charoff="50">8.1 ± 0.7</td><td align="center" valign="top" charoff="50">−42.6 ± 0.7</td><td align="center" valign="top" charoff="50">−7.2 ± 0.6</td></tr><tr><td align="center" valign="top" charoff="50">+</td><td align="center" valign="top" charoff="50">−3.0 ± 0.7</td><td align="center" valign="top" charoff="50">9.1 ± 0.7</td><td align="center" valign="top" charoff="50">−45.9 ± 0.8*</td><td align="center" valign="top" charoff="50">−8.4 ± 0.7</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Data are reported as mean ± SEM. *Indicates <italic>P</italic> < 0.05 compared to control using paired <italic>t</italic>-test.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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