Figure 5.

Activation of CaMKII is mediated by β₁-AR stimulation. (A) WT, β₁-AR KO, β₂-AR KO, and β₁-, β₂-AR double KO mice were administered with saline (NS), 5 mg/kg ISO, or 2.5 mg/kg 8-CPT by i.v. infusion for 5 min. LV homogenates were immunoblotted with anti-pCaMKII and anti-CaMKII antibodies. The CaMKII activation was quantified, expressed as fold increase over NS-treated WT mice, and shown as mean ± SEM (n = 5). Stimulation of β₁-AR but not β₂-AR activated CaMKII. *, P < 0.01 versus NS-treated WT mice; ^#, P < 0.01 versus ISO-treated WT mice. (B and C) HEK-293 cells stably expressing WT–β₁-AR (B) or WT–β₂-AR (C) were transiently transfected with CaMKII-δC and Flag-Epac1. Serum-starved cells were stimulated with either 10 µM ISO or 5 µM 8-CPT for the indicated times at 37°C (n = 5). Stimulation of β₁-AR by ISO markedly increased CaMKII activity over a period of time, whereas β₂-AR stimulation had no effect on CaMKII activation. IP, immunoprecipitation; T-CaMKII, total CaMKII.