L-cysteine prevents oxidation-induced block of the cardiac Na+ channel via interaction with heart-specific cysteinyl residues in the P-loop region
| Autor: | Norihito Sasaki, Yasutaka Yamamoto, Masaru Kato, Ryoji Kinugasa, Ichiro Hisatome, Toru Yatsuhashi, Yasutaka Kurata, Naomasa Makita, Koichi Matsubara, Masahiro Yamawaki, Kazuhide Ogino, Osamu Igawa, Kazuyoshi Ogura, Chiaki Shigemasa, Yasunori Tanaka |
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| Rok vydání: | 2002 |
| Předmět: |
Patch-Clamp Techniques
Homocysteine Sodium chemistry.chemical_element Sodium Channels chemistry.chemical_compound Methionine Medicine Humans Patch clamp Cysteine chemistry.chemical_classification Dose-Response Relationship Drug business.industry Sodium channel Myocardium fungi General Medicine Mercury Molecular biology chemistry Biochemistry Cell culture Thiol Cardiology and Cardiovascular Medicine business Oxidation-Reduction |
| Zdroj: | Circulation journal : official journal of the Japanese Circulation Society. 66(9) |
| ISSN: | 1346-9843 |
| Popis: | The present study investigated the protective effects of L-cysteine on the oxidation-induced blockade of Na+ channel a-subunits, hH1 (cardiac) and hSkM1 (skeletal), expressed in COS7 cells. Na+ currents were recorded by the whole-cell patch clamp technique (n = 3-7). L-cysteine alone blocked hH1 and hSkM1 in a dose-dependent manner, with saturating L-cysteine block at 3,000 micromol/L. Hg2+, a potent sulfhydryl oxidizing agent, blocked hH1 with a time to 50% inhibition (Time50%) of 20s. Preperfusion of COS7 cells with 100 micromol/L L-cysteine significantly slowed the Hg2+ block of hH1 (Time50% = 179 s). L-cysteine did not prevent Hg2+ block of hSkM1 (Time50% = 37s) or the C373Y hH1 mutant (Time50% = 43s). As for other sulfo-amino acids, homocysteine prevented the Hg2+ block of hH1, with the Time50% (70s) being significantly smaller than that of L-cysteine, whereas methionine did not prevent the Hg2+ block of hH1. L-cysteine did not prevent the Cd2+ block of hH1. These results indicate that L-cysteine selectively acts on heart-specific Cys373 in the P-loop region of hH1 to prevent Cys373 from the oxidation-induced sulfur-Hg-sulfur bridge formation. |
| Databáze: | OpenAIRE |
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