Molecular mechanisms of change in Ca^<2+>-sensitivity of muscle contraction induced by pH-reduction

pH降低引起的肌肉收缩Ca^2敏感性变化的分子机制

• 批准号: 07458222
• 负责人: OHTSUKI Iwao
• 金额: $ 4.74万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458222/
• 关键词: muscle contraction; Ca-sensitivity; acidosis; troponin; pH-sensitivity

The Ca^<2+>-sensitivity of contraction of striated muscles is lowered by reducing pH.The extent of this Ca^<2+>-sensitivity decrease is in the order of cardiac, fast skeletal and slow skeletal muscles. In order to examine the role of troponin C and I in this pH-dependent change in the Ca^<2+>-sensitivity, the effect of various hybrid combinations of troponin C and I from three kinds of striated muscles was studied on the Ca^<2+>-sensitive contraction of rabbit cardiac skinned fibers, using the troponin-exchange technique. As a result, the extent of the decrease in the Ca^<2+>-sensitivity on reducing pH was found to be in the following order :CC = FC > CF = FF > SC = SF (TnI・TnC)C,cardiac ; F,fast ; S,slowThese results clearly indicate that the change in the Ca^<2+>-sensitivity by pH-reduction is determined not only by the species of Ca^<2+>-receptive subunit (troponin C) but also by the interaction of troponin C with troponin I.Human cardiac troponin subunits were cloned, expressed in E.Coli and purified, and their action was investigated in skinned fibers. Involvement of troponin in the pH-sensitivity of Ca^<2+>-activated contraction of scallpo striated muscles was also demonstrated.

横纹肌收缩的Ca^<2+>敏感性随pH降低而降低，这种Ca^<2+>敏感性降低的程度按心肌、快骨骼肌和慢骨骼肌的顺序排列。为了检测肌钙蛋白C和I在Ca^2+敏感性的pH依赖性变化中的作用，采用肌钙蛋白交换技术研究了来自三种横纹肌的肌钙蛋白C和I的各种杂交组合对兔心脏皮肤纤维Ca^2+敏感性收缩的影响。结果表明，Ca^2+对pH降低的敏感性降低程度依次为：CC = FC > CF = FF > SC = SF（TnI·TnC）C，心脏; S、这些结果清楚地表明，pH降低引起的Ca^<2+>敏感性的变化不仅取决于Ca^<2+>感受亚基的种类克隆人心肌肌钙蛋白亚基，在大肠杆菌中表达并纯化，并研究其在皮肤纤维中的作用。肌钙蛋白参与了钙激活的横纹肌收缩的pH敏感性。

项目成果

I.Ohtsuki: Troponin components and Ca ion regulation of myofibrillar contraction in skeletal muscle.Calcium as cell signal (Igaku-shoin Tokyo), 36-42 (1995)

I.Ohtsuki：骨骼肌中肌原纤维收缩的肌钙蛋白成分和钙离子调节。钙作为细胞信号（Igaku-shoin Tokyo），36-42（1995）

I.Ohtsuki: "Troponin components and Ca ion regulation of myofibrillar contraction in skeletal muscle." Calcium as cell signal(Igaku-shoin Tokyo), 7 (1995)

I.Ohtsuki：“骨骼肌肌原纤维收缩的肌钙蛋白成分和 Ca 离子调节。”

S.Morimoto: "Reduced positive feedback regulation between myosin crossbridge and cardiac troponin C in fast skeletal myofibrils" J.Biochem.119(4). 737-742 (1996)

S.Morimoto：“快速骨骼肌原纤维中肌球蛋白横桥和心肌肌钙蛋白 C 之间的正反馈调节减少”J.Biochem.119(4)。

F.Shiraishi: "The inhibitory effect of troponin I on the ATPase activity of myofibrils treated with troponin T and troponin T_1" Fukuoka Acta Medica. 86(3). 89-91 (1995)

F.Shiraishi：“肌钙蛋白 I 对肌钙蛋白 T 和肌钙蛋白 T_1 处理的肌原纤维 ATP 酶活性的抑制作用”福冈医学学报。

I.Ohtsuki: "Troponin components and Ca icn regulation of myofibrillar contraction in skeletal muscle." Calcium as cell signal(Igaku-shoin Tokyo), 7 (1995)

I.Ohtsuki：“骨骼肌肌原纤维收缩的肌钙蛋白成分和 Ca2+ 调节。”