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

概要

論文の詳細を見る
The present study investigated the protective effects of L-cysteine on the oxidation-induced blockade of Na^+ channel ★-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,★mol/L. Hg^<2+>, a potent sulfhydryl oxidizing agent, blocked hH1 with a time to 50% inhibition (Time50%) of 20s. Preperfusion of COS7 cells with lOQ★mol/L Lcysteine significantly slowed the Hg^<2+> block of hH1 (Time50% = 179 s). L-cysteine did not prevent Hg^<2+> block of hSkM1 (Time50%=37 s) or the C373Y hH1 mutant (Time50%=43 s). As for other sulfo-amino acids, homocysteine prevented the Hg^<2+> block of hH1, with the Time50% (70 s) being significantly smaller than that of L-cysteine, whereas methionine did not prevent the Hg^<2+> block of hH1. L-cysteine did not prevent the Cd^<2+> block of hH1. These results indicate that L-cysteine selectively acts on heart-specific Cys^<373> in the P-loop region of hH1 to prevent Cys^<373> from the oxidation-induced sulfur-Hg-sulfur bridge formation.
社団法人日本循環器学会の論文
2002-08-20