Basic Research in Cardiology

, Volume 100, Issue 3, pp 250–262 | Cite as

Sorcin interacts with sarcoplasmic reticulum Ca2+–ATPase and modulates excitation–contraction coupling in the heart

  • T. Matsumoto
  • Y. HisamatsuEmail author
  • T. Ohkusa
  • N. Inoue
  • T. Sato
  • S. Suzuki
  • Y. Ikeda
  • M. Matsuzaki


Sorcin is a 21.6–kDa Ca2+ binding protein of the penta–EF hand family. Several studies have shown that sorcin modulates multiple proteins involved in excitation–contraction (E–C) coupling in the heart, such as the cardiac ryanodine receptor (RyR2), L–type Ca2+ channel, and Na+–Ca2+ exchanger, while it has also been shown to be phosphorylated by cAMP–dependent protein kinase (PKA). To elucidate the effects of sorcin and its PKA–dependent regulation on E–C coupling in the heart, we identified the PKA–phosphorylation site of sorcin, and found that serine178 was preferentially phosphorylated by PKA and dephosphorylated by protein phosphatase– 1. Isoproterenol allowed sorcin to translocate to the sarcoplasmic reticulum (SR). In addition, adenovirus–mediated overexpression of sorcin in adult rat cardiomyocytes significantly increased both the rate of decay of the Ca2+ transient and the SR Ca2+ load. An assay of oxalate–facilitated Ca2+ uptake showed that recombinant sorcin increased Ca2+ uptake in a dose–dependent manner. These data suggest that sorcin activates the Ca2+–uptake function in the SR. In UM–X7. 1 cardiomyopathic hamster hearts, the relative amount of sorcin was significantly increased in the SR fraction, whereas it was significantly decreased in whole–heart homogenates. In failing hearts, PKA–phosphorylated sorcin was markedly increased, as assessed using a back–phosphorylation assay with immunoprecipitated sorcin. Our results suggest that sorcin activates Ca2+–ATPase–mediated Ca2+ uptake and restores SR Ca2+ content, and may play critical roles in compensatory mechanisms in both Ca2+ homeostasis and cardiac dysfunction in failing hearts.

Key words

Sorcin excitation–contraction coupling Ca2+–ATPase (SERCA) sarcoplasmic reticulum PKA 


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Copyright information

© Steinkopff Verlag 2005

Authors and Affiliations

  • T. Matsumoto
    • 1
  • Y. Hisamatsu
    • 1
    Email author
  • T. Ohkusa
    • 1
  • N. Inoue
    • 1
  • T. Sato
    • 1
  • S. Suzuki
    • 1
  • Y. Ikeda
    • 2
  • M. Matsuzaki
    • 1
  1. 1.Division of Cardiovascular Medicine, Department of Medical Bioregulation Yamaguchi University Graduate, School of MedicineUbe Yamaguchi 755-8505Japan
  2. 2.Dept. of Molecular Cardiovascular Biology Yamaguchi University School of MedicineYamaguchi

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