In cardiomyocytes the cellular architecture is vastly different from that of heterologous cells, but until recently, the same principals and reliance on the CaVβ-subunit for surface trafficking were thought to apply, in part fueled by studies showing that short hairpin RNA-mediated knockdown of CaVβ2 reduced ICa in adult rat ventricular myocytes by ~60% [53], and others showing that CaVβ2−/− mice succumbed to embryonic lethality at around E10.5 due to heart failure caused by reduced L-type calcium current [18]. This evidence concerns the gene CACNB2 and heart failure.