Voigt et al. (2012) showed evidence of heightened Ca2+ spark frequency, increased opening probability of RyR2 and greater INCX in human AF myocytes. Inhibiting CaMKII was able to normalise the increased SR Ca2+ leak and reduce the opening probability of RyR2 (Voigt et al., 2012). As increased cytosolic Ca2+ activates forward-mode NCX, the authors suggest that the interplay between CaMKII, RyR2 and NCX results in the heightened Ca2+ spark frequency and DaDs in human AF myocytes. The gene discussed is TLX2; the disease is atrial fibrillation.