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• W2083434434 startingPage "G1105" @default.
• W2083434434 abstract "Hydrogen sulfide (H 2 S) is produced endogenously by l-cysteine metabolism. H 2 S modulates several ion channels with an unclear mechanism of action. A possible mechanism is through reduction-oxidation reactions attributable to the redox potential of the sulfur moiety. The aims of this study were to determine the effects of the H 2 S donor NaHS on Na V 1.5, a voltage-dependent sodium channel expressed in the gastrointestinal tract in human jejunum smooth muscle cells and interstitial cells of Cajal, and to elucidate whether H 2 S acts on Na V 1.5 by redox reactions. Whole cell Na + currents were recorded in freshly dissociated human jejunum circular myocytes and Na V 1.5-transfected human embryonic kidney-293 cells. RT-PCR amplified mRNA for H 2 S enzymes cystathionine β-synthase and cystathionine γ-lyase from the human jejunum. NaHS increased native Na + peak currents and shifted the half-point ( V 1/2 ) of steady-state activation and inactivation by +21 ± 2 mV and +15 ± 3 mV, respectively. Similar effects were seen on the heterologously expressed Na V 1.5 α subunit with EC 50 s in the 10 −4 to 10 −3 M range. The reducing agent dithiothreitol (DTT) mimicked in part the effects of NaHS by increasing peak current and positively shifting steady-state activation. DTT together with NaHS had an additive effect on steady-state activation but not on peak current, suggesting that the latter may be altered via reduction. Pretreatment with the Hg 2+ -conjugated oxidizer thimerosal or the alkylating agent N-ethylmaleimide inhibited or decreased NaHS induction of Na V 1.5 peak current. These studies show that H 2 S activates the gastrointestinal Na + channel, and the mechanism of action of H 2 S is partially redox independent." @default.
• W2083434434 created "2016-06-24" @default.
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• W2083434434 date "2011-06-01" @default.
• W2083434434 modified "2023-09-27" @default.
• W2083434434 title "Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5" @default.
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• W2083434434 doi "https://doi.org/10.1152/ajpgi.00556.2010" @default.
• W2083434434 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3119119" @default.
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• W2083434434 hasPublicationYear "2011" @default.
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