Regulation of the cardiac Na+/Ca2+ exchanger by calcineurin and protein kinase C

Munekazu Shigekawa, Yuki Katanosaka, Shigeo Wakabayashi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

19 Citations (Scopus)

Abstract

Na+/Ca2+ exchanger (NCX) activity is markedly inhibited in hypertrophic neonatal rat cardiomyocytes subjected to chronic phenylephrine treatment. This inhibition is reversed partially and independently by acute inhibition of calcineurin and protein kinase C (PKC) activities. Similar NCX inhibition occurs in CCL39 cells expressing cloned wildtype NCX1, when they are infected with adenoviral vectors carrying activated calcineurin A and then treated acutely with phorbol myristoyl acetate or protein phosphatase-1 inhibitors. The data obtained with these cells suggest that calcineurin activity, PKCα-mediated NCX1 phosphorylation, and the central loop of NCX1 (possibly its β1 repeat) are required for the observed NCX inhibition. We observe partial inhibition of NCX activity independent of NCX1 phosphorylation when CCL39 cells are infected with activated calcineurin A but not further treated with phorbol myristoyl acetate or phosphatase inhibitors. Calcineurin thus appears to downregulate NCX activity via two independent mechanisms, one involving NCX1 phosphorylation and the other not involving NCX1 phosphorylation. These data indicate the existence of a novel regulatory mechanism for NCX1 involving calcineurin and PKC, which may be important in cardiac pathology.

Original languageEnglish
Title of host publicationSodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion
Subtitle of host publicationFifth International Conference
PublisherBlackwell Publishing Inc.
Pages53-63
Number of pages11
ISBN (Print)1573316490, 9781573316491
DOIs
Publication statusPublished - Mar 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1099
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Calcineurin
  • Cardiac hypertrophy
  • Na/Ca exchanger
  • Phosphorylation
  • Protein kinase Cα

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Shigekawa, M., Katanosaka, Y., & Wakabayashi, S. (2007). Regulation of the cardiac Na+/Ca2+ exchanger by calcineurin and protein kinase C. In Sodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion: Fifth International Conference (pp. 53-63). (Annals of the New York Academy of Sciences; Vol. 1099). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1387.059