HCN4 and heart failure: Paradoxically, the sinus node in heart failure is like that in the athlete; there is intrinsic sinus bradycardia and a widespread remodeling of the sinus node with a downregulation of ion channels.43–45 miRs are known to function according to a combinatorial circuitry model, whereby a single miR targets multiple mRNAs and several coexpressed miRs may target a single mRNA.46 While our data suggest a prominent role for miR-423-5p in regulating HCN4, we cannot rule out a role for other miRs.