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000000003 005__ 20230824003248.0
000000003 0247_ $$a10.7936/K7J102MF$$2DOI
000000003 037__ $$aRDM
000000003 041__ $$aeng
000000003 245__ $$aDataset for Figure 1: Mechanisms of non-Covalent  Subunit Regulation of Nav Channel Gating and Pharmacology
000000003 269__ $$a2018-05-07
000000003 270__ $$mpopuluswendy@gmail.com$$pZhu, Wendy
000000003 300__ $$a268.5 MB
000000003 336__ $$aDataset
000000003 347__ $$babf
000000003 347__ $$bxlsx
000000003 347__ $$bpdf
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000000003 520__ $$aVoltage-gated Na+ (NaV) channels comprise a macromolecular complex, whose members tailor their function according to cell type. Key members are the non-covalently bound NaV 1 and 3 subunits that regulate channel gating, expression, and pharmacology. To probe the molecular basis of this regulation, we applied voltage-clamp fluorometry to measure how the subunits affect conformations within the cardiac NaV channel (NaV1.5) voltage-sensing domains (VSDs). The pore-forming NaV1.5-subunit contains four domains (DI-DIV), each with a VSD. Our results show that 1 and 3 regulate NaV1.5 by altering DIII- and DIV-VSD activation, an interaction that is significantly altered by atrial fibrillation-variants in both subunits. 1 and 3 strongly affected the interaction of Class Ib anti-arrhythmic drugs, lidocaine and ranolazine, with the DIII-VSD. Our results demonstrate that 1 and 3 regulation of the NaV1.5 VSDs can significantly determine NaV1.5 pathology and its therapeutic response.
000000003 536__ $$c15PRE25080073$$oAmerican Heart Association$$qhttps://ror.org/013kjyp64
000000003 536__ $$aBurroughs Wellcome Fund Career Award at the Scientific Interface$$c1010299$$oBurroughs Wellcome Fund$$qhttps://ror.org/01d35cw23
000000003 540__ $$aCreative Commons Attribution (CC BY) 4.0 International$$uhttps://creativecommons.org/licenses/by/4.0/
000000003 650__ $$aMedical engineering
000000003 6531_ $$abiomedical engineering
000000003 655__ $$aTabular
000000003 7001_ $$aZhu, Wendy$$uWashington University in St. Louis$$4https://ror.org/01yc7t268$$5ROR
000000003 7001_ $$aSilva, Jonathan R.$$1https://orcid.org/0000-0002-3696-3955$$uWashington University in St. Louis$$4https://ror.org/01yc7t268$$5ROR
000000003 791__ $$tZhu W, Voelker TL, Varga Z, Schubert AR, Nerbonne JM, Silva JR. Mechanisms of noncovalent β subunit regulation of NaV channel gating. The Journal of General Physiology. 2017. 149(8):813-831.$$aJournalArticle$$eIsSupplementTo$$whttps://doi.org/10.1085/jgp.201711802$$2DOI
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000000003 8564_ $$9b1bd0b27-9a0e-4d74-a35b-89407e0ef750$$s260934360$$uhttps://data.library.wustl.edu/record/3/files/Silva_Figure1.zip$$ePublic$$2d3266e8cc315d46df4481747da2a57ef$$01
000000003 904__ $$ajonsilva@gmail.com
000000003 909CO $$ooai:data.library.wustl.edu:3$$pdataset
000000003 980__ $$aWashU Researcher Data