Remodeling of excitation-contraction coupling in the heart: inhibition of sarcoplasmic reticulum Ca(2+) leak as a novel therapeutic approach.
In the heart, excitation-contraction coupling is the central mechanism by which electrical activation is translated into cardiac contraction. In heart failure, several proteins involved in this finely concerted regulation are changed with respect to expression, phosphorylation status, and function leading to remodeling of excitation-contraction coupling. The present review article summarizes well known alterations in heart failure and focuses on recent findings especially regarding altered sarcoplasmic reticulum Ca(2+) release process due to two distinct kinases, namely protein kinase A and Ca(2+)/calmodulin-dependent kinase II. Furthermore, it highlights the translation of those findings into possible novel therapeutic approaches.
Neef
Stefan
S
Abteilung Kardiologie und Pneumologie/Herzzentrum, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Maier
Lars S
LS
D000200:Action Potentials; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology
D015220:Calcium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases