RYR2 and hydrops fetalis: Interestingly, through their mechanism of action, β-blockers also inhibit PKA hyperphosphorylation of the RyR2 channel in both human and animal models of HF (Reiken et al., 2001, 2003); the proposed mechanism by which β-blockers improve cardiac function in HF is by preventing PKA hyperphosphorylation of RyR2 Ser2808 and subsequent receptor destabilization (Shan et al., 2010).