Review of forty years of studies on Ca<sup>2+</sup> homeostasis in myocytes

  • OGAWA YASUO
    Department of Pharmacology, Juntendo University School of Medicine

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  • 筋細胞におけるCa<sup>2+</sup>homeostasis研究40年を顧みて
  • 筋細胞におけるCa〔2+〕 homeostasis研究40年を顧みて
  • キン サイボウ ニ オケル Ca 2 homeostasis ケンキュウ 40ネン オ カエリミテ

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The free Ca2+ concentration in the sarcoplasm is about 0.1 μM at rest, whereas the extracellular Ca2+ concentration is about 1 mM. Activation of myocytes causes a transient increase of the sarcoplasmic Ca2+ to several μM, resulting in triggered activities including muscle contraction. Here, I first review our achievements in characterization of Ca2+ buffers (EGTA, Ca2+ dyes, troponin C, calmodulin and parvalbumins) with the implications of those results. Then, the transient kinetics of Ca2+ pump and EP formation are discussed in reference to the rate of muscle relaxation. Finally, our recent studies on the properties of ryanodine receptor isoforms (Ca2+ releasing channels) are described. The gain for CICR of RyR1 is suppressed in the SR from wildtype animals, whereas the suppression is absent in the mutant expressing the malignant hyperthermia. A minor contribution of CICR to EC coupling is shown in skeletal muscles, and a new approach with line-scan imaging of a multicellular system of a papillary muscle has proved to be effective for elucidation of the mechanisms underlying ventricular arrhythmia.

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