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dc.contributor.authorBosmans, Frank
dc.contributor.authorPuopolo, Michelino
dc.contributor.authorMartin-Eauclaire, Marie-France
dc.contributor.authorBean, Bruce Palmer
dc.contributor.authorSwartz, Kenton J.
dc.date.accessioned2013-02-14T21:47:19Z
dc.date.issued2011
dc.identifier.citationBosmans, Frank, Michelino Puopolo, Marie-France Martin-Eauclaire, Bruce P. Bean, and Kenton J. Swartz. 2011. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors. The Journal of General Physiology 138(1): 59-72.en_US
dc.identifier.issn0022-1295en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10303290
dc.description.abstractThe voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage sensors to channel function and pharmacology. We define individual S3b–S4 paddle motifs within each voltage sensor, and show that they can sense changes in membrane voltage and drive voltage sensor activation when transplanted into voltage-activated potassium channels. We also find that the paddle motifs in Nav1.9 are targeted by animal toxins, and that these toxins alter Nav1.9-mediated currents in DRG neurons. Our results demonstrate that slowly activating and inactivating Nav1.9 channels have functional and pharmacological properties in common with canonical Nav channels, but also show distinctive pharmacological sensitivities that can potentially be exploited for developing novel treatments for pain.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1085/jgp.201110614en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135324/pdf/en_US
dash.licenseLAA
dc.titleFunctional Properties and Toxin Pharmacology of a Dorsal Root Ganglion Sodium Channel Viewed through its Voltage Sensorsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of General Physiologyen_US
dash.depositing.authorBean, Bruce Palmer
dc.date.available2013-02-14T21:47:19Z
dc.identifier.doi10.1085/jgp.201110614*
dash.contributor.affiliatedBean, Bruce


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