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Intracellular Calcium Release Channels in Muscles Related to Excitation-Contraction-Coupling and Malignant Hyperthermia

  • Makoto Endo
Conference paper

Abstract

A plant alkaloid, ryanodine, was found to act specifically on intracellular Ca release channels, fixing them in the open state, only when the channels were open [1]. Utilizing the specific action of ryanodine, the channel protein was isolated, purified [2–4], and sequenced [5]. The purified channel protein showed all the properties of the Ca-induced Ca release (CICR) channel [3,4,6]; activation by Ca, acceleration of opening by ATP, inhibition of opening by Mg, and so on. Morphologically, the channel appeared to be very similar to the foot structure at the triad junction [2,4], which is considered to be the physiological Ca release channel. Curiously enough, however, CICR does not seem to be the mechanism of physiological Ca release. It is likely that the Ca release channel in skeletal muscle operates in different modes when stimulated through the physiological pathway (depolarization of the T-tubule membrane, probably through changes in voltage sensor molecules) and when stimulated by increased Ca ion concentration (CICR). Although the CICR opening mode does not seem to be important physiologically, it is important pathophysiologically, as in malignant hyperthermia (MH), and pharmacologically, as in caffeine contracture. These two opening modes are pharmacologically different; procaine and adenine inhibit the CICR mode, but not the physiological mode [7]. An interesting agent is dantrolene; it inhibits both modes to an almost equal extent at 37°C, but at 20°C the agent does not inhibit the CICR mode at all, whereas it still effectively inhibits the physiological mode [8].

Keywords

Sarcoplasmic Reticulum Release Channel Malignant Hyperthermia Malignant Hyperthermia Physiological Mode 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Fleischer S, Ogunbunmi EM, Dixon MC, Fleer EA (1985) Localization of Ca2+ release channels with ryanodine in junctional terminal cisternae of sarcoplasmic reticulum of fast skeletal muscle. Proc Natl Acad Sci USA 82: 7256–7259PubMedCrossRefGoogle Scholar
  2. 2.
    Inui M, Saito A, Fleischer S (1987) Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem 262: 1740–1747PubMedGoogle Scholar
  3. 3.
    Imagawa T, Smith JS, Coronado R, Campbell KP (1987) Purified ryanodine receptor from skeletal muscle sarcoplasmic reticulum is the Cat+-permeable pore of the calcium release channel. J Biol Chem 262: 16636–16643PubMedGoogle Scholar
  4. 4.
    Lai FA, Erickson HP, Rousseau E, Liu Q-Y, Meissner G (1988) Purification and reconstitution of the calcium release channel from skeletal muscle. Nature 331: 315–319PubMedCrossRefGoogle Scholar
  5. 5.
    Takeshima H, Nishimura S, Matsumoto T, Ishida H, Kangawa K, Minamino N, Matsuo H, Ueda M, Hanaoka M, Hirose T, Numa S (1989) Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 339: 439–445PubMedCrossRefGoogle Scholar
  6. 6.
    Hymel L, Inui M, Fleischer S, Schindler HG (1988) Purified ryanodine receptor of skeletal muscle forms Ca2+-activated oligomeric Ca2+ channels in planar bilayers. Proc Natl Acad Sci USA 85: 441–445PubMedCrossRefGoogle Scholar
  7. 7.
    Endo M (1985) Calcium release from sarcoplasmic reticulum. Curr Top Membr Transp 25: 181–230CrossRefGoogle Scholar
  8. 8.
    Kobayashi T, Endo M (1988) Temperature-dependent inhibition of caffeine contracture of mammalian skeletal muscle by dantrolene. Proc Japan Acad 64: 76–79CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1996

Authors and Affiliations

  • Makoto Endo
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicineUniversity of TokyoBunkyo-ku, Tokyo, 113Japan

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