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Data from this and other research groups consistently demonstrated that in failing CMs, s2-ARs are uncoupled from the localized pools of PKA,leroy which are physiologically targeted within the 2-AR/cAMP signaling compartment and, consequently, activation of 2-AR leads, in failing cells, to a wide cAMP propagation pattern similar to that observed in normal CMs upon 1-AR stimulation (Calaghan et al., 2008