Regions of heterogeneous Cx43 expression and gap junction conductance have been described in infarcted and failing hearts (Poelzing and Rosenbaum, 2004; Cabo et al., 2006; Akar et al., 2007), can lead to source/sink mismatch and block of propagation (Kleber and Rudy, 2004), and are likely to provide the “substrate” that leads to initiation of cardiac arrhythmias in diseased hearts. This evidence concerns the gene GJA1 and cardiac arrhythmia.