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. Author manuscript; available in PMC: 2010 Jul 12.
Published in final edited form as: Cell. 2005 Oct 7;123(1):25–35. doi: 10.1016/j.cell.2005.07.030

Figure 6. Cardiac Arrhythmias due to PDE4D3 Inhibition Are Suppressed in Mice Harboring Mutant RyR2 that Cannot be PKA Phosphorylated.

Figure 6

(A) Susceptibility to exercise-induced sustained ventricular arrhythmias (sVT) and nonsustained ventricular arrhythmias (nsVT) was significantly increased in PDE4D−/− compared to wt mice (each n = 6, *p < 0.05).

(B) Rolipram (0.3 mg/kg body weight) maximally increased RyR2-Ser2808 PKA phosphorylation during exercise in vivo. Treatment as indicated on top: Rol, rolipram; Epi, epinephrine (0.1 mg/kg); white bars, no rolipram; black bar, rolipram-treated mice; *p < 0.05 between treatments in wt mice; #p < 0.001 wt versus homozygous RyR2-S2808A knockin (S2808A+/+) mice. Control mice were treated with placebo (rolipram carrier, 0.5% DMSO). Data are mean ± SD.

(C) In rolipram-treated mice, susceptibility to exercise-induced sustained ventricular arrhythmias (sVT) and nonsustained ventricular arrhythmias (nsVT) was significantly decreased in homozygous RyR2-S2808A knockin (S2808A+/+) mice compared to wt mice (each n = 6, #p < 0.05).

(D) Mortality from sudden death was significantly increased in PDE4D+/− mice 24 and 72 hr after MI compared to wt mice. White bars, wt mice; black bars, PDE4D+/− mice. *p < 0.01 between wt and PDE4D+/− groups.