Voltage-dependent L-type calcium channels (LTCCs) transport Ca2+ into excitable cells. Isoforms CACNA1C, D, F and S form long-lasting (L-type) inward Ca2+ currents (ICaL) and play an important role in excitation-contraction coupling in the heart. LTCCs are multisubunit complexes consisting of alpha-1, alpha-2, beta, delta and gamma subunits in a 1:1:1:1:1 ratio (Brust et al. 1993). The alpha-2 and beta subunits in these complexes are chains of differing length cleaved from the same gene products (CACNA2D1, 2, 3 and 4), linked by a disulfide bond (Calderon-Rivera et al. 2012). Pore-forming alpha1 subunits are supported by the auxiliary alpha-2, delta and beta subunits which aid the membrane trafficking of the alpha1 subunit and modulate the kinetic properties of the channel (Klugbauer et al. 2003). The binding of various gamma subunits to alpha1 subunits may differentially modulate alpha1 subunit function in the heart (Yang et al. 2011). In heart pacemaker cells, phase 0 of the action potential depends upon LTCC-mediated Ca2+ current rather than the fast Na+ current. In cardiac pacemaker cells, phase 1 is due to the closure of LTCCs (and rapid efflux of K+).