Premium
Regulation of the Cardiac Na + /Ca 2+ Exchanger by Calcineurin and Protein Kinase C
Author(s) -
SHIGEKAWA MUNEKAZU,
KATANOSAKA YUKI,
WAKABAYASHI SHIGEO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.059
Subject(s) - calcineurin , protein kinase c , phosphorylation , phosphatase , chemistry , phorbol , microbiology and biotechnology , biology , medicine , biochemistry , transplantation
Na + /Ca 2+ 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 wild‐type 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.