Hyperphosphorylation of the Cardiac Ryanodine Receptor at Serine 2808 Is Not Involved in Cardiac Dysfunction After Myocardial Infarction

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Abnormal behavior of the cardiac ryanodine receptor (RyR2) has been linked to cardiac arrhythmias and heart failure (HF) after myocardial infarction (MI). It has been proposed that protein kinase A (PKA) hyperphosphorylation of the RyR2 at a single residue, Ser-2808, is a critical mediator of RyR dysfunction, depressed cardiac performance, and HF after MI.


We used a mouse model (RyRS2808A) in which PKA hyperphosphorylation of the RyR2 at Ser-2808 is prevented to determine whether loss of PKA phosphorylation at this site averts post MI cardiac pump dysfunction.

Methods and Results:

MI was induced in wild-type (WT) and S2808A mice. Myocyte and cardiac function were compared in WT and S2808A animals before and after MI. The effects of the PKA activator Isoproterenol (Iso) on L-type Ca2+ current (ICaL), contractions, and [Ca2+]I transients were also measured. Both WT and S2808A mice had depressed pump function after MI, and there were no differences between groups. MI size was also identical in both groups. L type Ca2+ current, contractions, Ca2+ transients, and SR Ca2+ load were also not significantly different in WT versus S2808A myocytes either before or after MI. Iso effects on Ca2+ current, contraction, Ca2+ transients, and SR Ca2+ load were identical in WT and S2808A myocytes before and after MI at both low and high concentrations.


These results strongly support the idea that PKA phosphorylation of RyR-S2808 is irrelevant to the development of cardiac dysfunction after MI, at least in the mice used in this study.

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