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Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Phosphorylation of RyR2 Ser-2814 by CaMKII mediates β1-adrenergic stress induced Ca2+-leak from the sarcoplasmic reticulum
FEBS Open Bio  (IF2.693),  Pub Date : 2021-08-17, DOI: 10.1002/2211-5463.13274
Maria J. Baier, Jannis Noack, Mark Tilmann Seitz, Lars S. Maier, Stefan Neef

Adrenergic stimulation, while being the central mechanism of cardiac positive inotropy, is a universally acknowledged inductor of undesirable sarcoplasmic reticulum (SR) Ca2+ leak. However, the exact mechanisms for this remained unspecified so far. This study shows that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-specific phosphorylation of ryanodine receptor type 2 at Ser-2814 is the pivotal mechanism by which SR Ca2+ leak develops downstream of β1-adrenergic stress by increase of the leak/load relationship. Cardiomyocytes with a Ser-2814 phosphoresistant mutation (S2814A) were protected from isoproterenol-induced SR Ca2+ leak and consequently displayed improved postrest potentiation of systolic Ca2+ release under adrenergic stress compared to littermate wild-type cells.