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• W2169726777 abstract "Rat descending vasa recta (DVR) express a tetrodotoxin (TTX)-sensitive voltage-operated Na + (Na V ) conductance. We examined expression of Na V isoforms in DVR and tested for regulation of Na V currents by calmodulin (CaM). RT-PCR in isolated permeabilized DVR using degenerate primers targeted to TTX-sensitive isoforms amplified a product whose sequence identified only Na V 1.3. Immunoblot of outer medullary homogenate verified Na V 1.3 expression, and fluorescent immunochemistry showed Na V 1.3 expression in isolated vessels. Immunochemistry in outer medullary serial sections confirmed that Na V 1.3 is confined to α-smooth muscle actin-positive vascular bundles. Na V 1.3 possesses a COOH-terminal CaM binding motifs. Using pull-down assays and immunoprecipitation experiments, we verified that CaM binds to either full-length Na V 1.3 or a GST-Na V 1.3 COOH-terminal fusion protein. In patch-clamp experiments, Na V currents were suppressed by calmodulin inhibitory peptide (CIP; 100 nM) or the CaM inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene-sulphonamide hydrochloride (W7). Neither CIP nor W7 altered the voltage dependence of pericyte Na V currents; however, raising electrode free Ca 2+ from 20 to ∼2,000 nM produced a depolarizing shift of activation. In vitro binding of CaM to GST-Na V 1.3C was not affected by Ca 2+ concentration. We conclude that Na V 1.3 is expressed by DVR, binds to CaM, and is regulated by CaM and Ca 2+ . Inhibition of CaM binding suppresses pericyte Na V currents." @default.
• W2169726777 created "2016-06-24" @default.
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• W2169726777 date "2007-01-01" @default.
• W2169726777 modified "2023-10-15" @default.
• W2169726777 title "Vasa recta voltage-gated Na⁺channel Na_v1.3 is regulated by calmodulin" @default.
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• W2169726777 doi "https://doi.org/10.1152/ajprenal.00070.2006" @default.
• W2169726777 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16912065" @default.
• W2169726777 hasPublicationYear "2007" @default.
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