title: Intracellular Ca2+ store in embryonic cardiac myocytes.
abstract: In mature cardiac myocytes, Ca2+ influx through the L-type Ca2+ channel activates the ryanodine receptor and triggers Ca2+ release from the sarcoplasmic reticulum (SR). This Ca2+ signal amplification, termed Ca2+-induced Ca2+ release (CICR), occurs within the junctional membrane complex between the plasma membrane and the SR, and is essential for cardiac excitation-contraction (E-C) coupling. On the other hand, Ca2+ available during E-C coupling is predominantly derived from Ca2+ influx in embryonic cardiac myocytes. To examine the role of the intracellular Ca2+ store in immature cardiac myocytes, we have generated knockout mice lacking the cardiac type of the ryanodine receptor (RyR-2), or junctophilin (JP-2) contributing to formation of the junctional membrane complex. Both RyR-2- and JP-2-knockout mice show lethality at early embryonic stages immediately after beginning of heart beating. The loss of RyR-2 produced abnormal SR elements exhibiting vacuolated structures and Ca2+-overloading in embryonic cardiac myocytes. In JP-2-deficient cardiac myocytes, formation of junctional membrane complexes, called pheripheral couplings, was disturbed, and abnormal Ca2+ transients without spatial and temporal synchronization were observed. Therefore, the knockout mice have demonstrated that RyR-2-mediated Ca2+ release at the junctional membrane complex is essential for cellular Ca2+ homeostasis in immature cardiac myocytes.
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Miyagi 980-8575, Japan. takeshim@mail.cc.tohoku.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D004622:Embryo, Mammalian / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*
chemical_list: D002118:Calcium