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. 2010 Nov 22;120(12):4388–4398. doi: 10.1172/JCI32726

Figure 1. PKA phosphorylation of RyR2 mediates the chronotropic and inotropic response to β-adrenergic activation.

Figure 1

Cardiac contractility and heart rate were measured in vivo using left ventricular catheterization in response to low-dose (2 μg/kg i.p.) and high-dose (2 mg/kg i.p.) Iso. (A) Contractility reported as dP/dtmax. (B) Heart rate in bpm. Dashed lines indicate the points at which Iso was administered i.p. (WT, n = 5; RyR2-S2808A+/+, n = 6; *P < 0.05, versus WT). (C) Representative immunoblot analyses of RyR2 immunoprecipitates (from 100 μg of cardiac lysates), using phosphoepitope-specific antibodies that detect PKA-phosphorylated RyR2-Ser2808 (pS2808), CaMKII-phosphorylated RyR2-Ser2814 (pS2814), oxidation of RyR2 (DNP), and calstabin2 associated with the channel. (D) Representative immunoblot of CSR treated with hydrogen peroxide (H2O2) plus either PKA or CaMKII and levels of calstabin2 associated with the channel. S2808A, RyR2-S2808A+/+.