A Mutant of TTX-Resistant Cardiac Sodium Channels with TTX-Sensitive Properties

DOI Web Site 被引用文献6件
  • Jonathan Satin
    Laboratory of Cardiac Electrophysiology, Departments of Medicine and Pharmacological and Physiological Sciences, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • John W. Kyle
    Laboratory of Molecular Neuro-Cardiology, Department of Medicine, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • Michael Chen
    Laboratory of Molecular Neuro-Cardiology, Department of Medicine, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • Peter Bell
    Laboratory of Molecular Neuro-Cardiology, Department of Medicine, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • Leanne L. Cribbs
    Laboratory of Molecular Neuro-Cardiology, Department of Medicine, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • Harry A. Fozzard
    Laboratory of Cardiac Electrophysiology, Departments of Medicine and Pharmacological and Physiological Sciences, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637
  • Richard B. Rogart
    Laboratory of Molecular Neuro-Cardiology, Department of Medicine, and The Committee on Cell Physiology, The University of Chicago, MC-6094, 5841 South Maryland Avenue, Chicago, IL 60637

抄録

<jats:p>The cardiac sodium channel α subunit (RHI) is less sensitive to tetrodotoxin (TTX) and saxitoxin (STX) and more sensitive to cadmium than brain and skeletal muscle (μl) isoforms. An RHI mutant, with Tyr substituted for Cys at position 374 (as in μl) confers three properties of TTX-sensitive channels: (i) greater sensitivity to TTX (730-fold); (ii) lower sensitivity to cadmium (28-fold); and (iii) altered additional block by toxin upon repetitive stimulation. Thus, the primary determinant of high-affinity TTX-STX binding is a critical aromatic residue at position 374, and the interaction may take place possibly through an ionized hydrogen bond. This finding requires revision of the sodium channel pore structure that has been previously suggested by homology with the potassium channel.</jats:p>

収録刊行物

  • Science

    Science 256 (5060), 1202-1205, 1992-05-22

    American Association for the Advancement of Science (AAAS)

被引用文献 (6)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ