L-Cysteine Prevents Oxidation-Induced Block of the Cardiac Na+ Channel Via Interaction With Heart-Specific Cysteinyl Residues in the P-Loop Region.

Yatsuhashi, Toru; Hisatome, Ichiro; Kurata, Yasutaka; Sasaki, Norihito; Ogura, Kazuyoshi; Kato, Mamoru; Kinugasa, Ryoji; Matsubara, Koichi; Yamawaki, Masahiro; Yamamoto, Yorihiro; Tanaka, Yasunori; Oginö, Kazuhíde; Igawa, Osamu; Makita, Naomasa; Shigemasa, Chiaki

doi:10.1253/circj.66.846

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…In guinea pig and human colon, Cl Ϫ secretion stimulated by NaHS and L-cysteine was blocked by TTX, but NaHS-induced Cl Ϫ secretion was not found in T84 human colon epithelial cells, suggesting that TTX-sensitive Na ϩ channels may be necessary for H 2 S-stimulated Cl Ϫ secretion (33,42). TTX-sensitive and TTX-resistant Na ϩ channels have different sensitivities but generally not opposite effects in response to L-cysteine, taurine, or redox reagents (Table 1; 37,49,50). Because H 2 S was shown to be an activator of TTX-resistant Na V 1.5 in our study, the interrelationship between H 2 S, Na V 1.5, and Cl Ϫ channels in the gastrointestinal tract deserves study.…”

Section: Discussionmentioning

confidence: 99%

“…H 2 S and alternative byproducts of cysteine metabolism appear to have potency as redox reagents (46,50) and can affect both TTX-resistant and TTX-sensitive Na ϩ channels. For example, L-cysteine (0.1 mM) prevents inhibition of peak Na V 1.5 current by the oxidizing ion Hg 2ϩ but not Cd 2ϩ in hH1-transfected COS7 cells (49). Cysteine oxidized as cysteic acid can be decarboxylated into taurine.…”

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confidence: 99%

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Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Strege

Bernard

Kraichely

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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gen sulfide (H 2S) is produced endogenously by L-cysteine metabolism. H 2S 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 2S donor NaHS on Na V1.5, 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 2S acts on NaV1.5 by redox reactions. Whole cell Na ϩ currents were recorded in freshly dissociated human jejunum circular myocytes and Na V1.5-transfected human embryonic kidney-293 cells. RT-PCR amplified mRNA for H 2S enzymes cystathionine ␤-synthase and cystathionine ␥-lyase from the human jejunum. NaHS increased native Na ϩ peak currents and shifted the half-point (V 1/2) of steady-state activation and inactivation by ϩ21 Ϯ 2 mV and ϩ15 Ϯ 3 mV, respectively. Similar effects were seen on the heterologously expressed Na V1.5 ␣ subunit with EC50s in the 10 Ϫ4 to 10 Ϫ3 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 2ϩ -conjugated oxidizer thimerosal or the alkylating agent N-ethylmaleimide inhibited or decreased NaHS induction of NaV1.5 peak current. These studies show that H2S activates the gastrointestinal Na ϩ channel, and the mechanism of action of H2S is partially redox independent. patch clamp; intestine; smooth muscle; dithiothreitol; thimerosal HYDROGEN SULFIDE (H 2 S) IS A GAS produced endogenously through L-cysteine metabolism predominantly by two enzymes, cystathione ␥-lyase (CSE) and cystathione ␤-synthase (CBS) (reviewed in Refs. 4,14,19). H 2 S is detected in mammalian tissues and in circulation. Moreover, H 2 S and/or HS Ϫ have been shown to be an active molecule, with clear pharmacological effects on smooth muscle tissues, including relaxation of vascular, corpus cavernosum, uterine, and gastrointestinal smooth muscle.Ion channels regulate contractility of gastrointestinal smooth muscle. H 2 S is known to target various ion channels. Evidence for this involvement of channel activity is strongest for the K ATP channel with some evidence for modulation of BK, Cl Ϫ , and L-type and T-type Ca 2ϩ channels (15,19,42). In human intestinal smooth muscle cells, channels that allow entry of ions into the cell include Na V 1.5 [Na ϩ current: (10, 27, 38, 48), Ca V 1.2 L-type Ca 2ϩ current: (6, 7, 22, 47), Ca V 3.2 T-type Ca 2ϩ current: (8, 47)], and nonselective cation channels (16). The mechanism by which H 2 S modulates ion-channel activity is still largely unknown, and, although the chemistry of H 2 S favors redox modification of proteins, there has been little study of this effect. H 2 S and alterna...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Strege

Bernard

Kraichely

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…ES-cell-derived cardiac precursor cells were purified from the EBs using GFP as a reporter as described by Hidaka et al 5 Action potentials and T-type Ca 2+ currents from the Nkx2.5/GFP(+) cells were recorded using perforated patch-clamp and standard voltage-clamp techniques. 6,7 The effects of various drugs on the automaticity of Nkx2.5/GFP(+) cells were tested in the early (≤8 after differentiation), intermediate (days [9][10][11][12][13][14][15][16][17][18][19] and late stages (≥day 20) of differentiation as described by …”

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Developmental Changes of Ni2+ Sensitivity and Automaticity in Nkx2.5-Positive Cardiac Precursor Cells From Murine Embryonic Stem Cell

Manabe

Miake

Sasaki

et al. 2004

Circ J

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“…Forty-eight h after transfection, cells were visualized by EGFP fluorescence and subjected to the whole-cell patch clamp experiments. 16 …”

Section: Plasmid and Expressionmentioning

confidence: 99%

State-Dependent Blocking Actions of Azimilide Dihydrochlo-ride (NE-10064) on Human Cardiac Na+ Channels

Miake

Kurata

Iizuka

et al. 2004

Circ J

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zimilide dihydrochloride (NE-10064), a chlorphenylfranyl compound, prolongs cardiac refractoriness by blocking the fast (IKr) and slow (IKs) components of the delayed-rectifier potassium currents. [1][2][3] These in vitro electrophysiologic properties of azimilide could account for its antiarrhythmic and antifibrillatory actions in a number of animal models, which could be classified as class III antiarrhythmic actions. [4][5][6][7][8][9][10] It has been reported that azimilide interacts with other cardiac ion channels, blocking the L-type Ca 2+ channel, the inward rectifier K + channel, and the Na + channel, 11-13 but so far there have not been any systematic studies of the effects of azimilide on the cardiac Na + channels and little is known about the statedependent azimilide block of the Na + channels, although a few reports indicated that azimilide blocked cardiac peak Circulation Journal Vol. 68, July 2004 and late Na + currents. 12-15 Therefore, we assessed the effects of azimilide on the Na + current using the wild-type -subunit of the human cardiac sodium channel (hH1: WT) as well as long QT syndrome type III mutant (∆KPQ mutant) expressed in COS7 cells. Methods Plasmid and ExpressionThe vector pRC/CMV (Invitrogen, San Diego, CA, USA) was used as the expression vector for human WT or ∆KPQ mutant cDNAs. COS7 cells were maintained in Dulbecco's modified Eagle medium (DMEM; Gibco BRL, Gaithersburg, MD, USA)/10% fetal bovine serum, 1% penicillin and 1% streptomycin at 37°C in a 5% CO2 incubator. Cells grown on glass coverslips were co-transfected with both pRC/WT or pRC/∆KPQ mutant and pEGFPC1 (Clontech, Palo Alto, CA, USA) by using Lipofectamine (Gibco BRL) according to the manufacturer's instructions. Forty-eight h after transfection, cells were visualized by EGFP fluorescence and subjected to the whole-cell patch clamp experiments. 16 Electrophysiological RecordingsWhole-cell patch clamp experiments were performed at 22°C. The external solution had the following composition ( mol/L): NaCl 140, CsCl 5.0, MgCl2 1.0, CaCl2 1.8, HEPES 10 and glucose 10, pH 7.4 with NaOH. Patch clamp electrodes were filled with a solution of the following composition ( mol/L): CsF 90, CsCl 10, EGTA 10, NaF 10, MgCl2 2 and HEPES 10, pH 7.4 with CsOH.Currents were recorded with a patch clamp amplifier (Axopatch). The membrane current was filtered at 10 kHz

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L-Cysteine Prevents Oxidation-Induced Block of the Cardiac Na+ Channel Via Interaction With Heart-Specific Cysteinyl Residues in the P-Loop Region.

Cited by 7 publications

References 25 publications

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Developmental Changes of Ni2+ Sensitivity and Automaticity in Nkx2.5-Positive Cardiac Precursor Cells From Murine Embryonic Stem Cell

State-Dependent Blocking Actions of Azimilide Dihydrochlo-ride (NE-10064) on Human Cardiac Na+ Channels

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L-Cysteine Prevents Oxidation-Induced Block of the Cardiac Na+ Channel Via Interaction With Heart-Specific Cysteinyl Residues in the P-Loop Region.

Cited by 7 publications

References 25 publications

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na+ channel, Nav1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na+ channel, Nav1.5

Developmental Changes of Ni2+ Sensitivity and Automaticity in Nkx2.5-Positive Cardiac Precursor Cells From Murine Embryonic Stem Cell

State-Dependent Blocking Actions of Azimilide Dihydrochlo-ride (NE-10064) on Human Cardiac Na+ Channels

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Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5

Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na⁺ channel, Na_v1.5