Toward biologically targeted therapy of calcium cycling defects in heart failure.
A growing body of evidence indicates that heart failure progression is tightly associated with dysregulation of phosphorylation of Ca2+ regulators localized in the sub-cellular microdomain of the sarcoplasmic reticulum. Chemical or genetic correction of abnormalities in cardiac phosphorylation cascades is emerging as a potential target in the treatment of heart failure. Here, we review how specific kinases and phosphatases finely tune Ca2+ cycling and regulate excitation-contraction (E-C) coupling in cardiomyocytes.
Ikeda
Yasuhiro
Y
Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, Ube, Japan. ysikeda@yamaguchi-u.ac.jp
Hoshijima
Masahiko
M
Chien
Kenneth R
KR
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018450:Disease Progression; D015316:Genetic Therapy / Q000379:methods*; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1 / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D002316:Cardiotonic Agents; D019837:Ryanodine Receptor Calcium Release Channel; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054645:Protein Phosphatase 1; D010744:Phosphoric Monoester Hydrolases