Schematic of Ca v1.2 α 1C and β 2B subunits and proposed mechanism of Rad regulation. (A) Basal ICa,L is inhibited by Rad, an effect dependent on an interaction with β2B and association of Rad with the t-tubular membrane. The lipid interaction depends on helix 8, a polybasic region of the C-terminus. (B) Truncation of the Rad C-terminus by introducing a stop codon at Ala277 dissociates Rad from the t-tubule membrane and relieves ICa,L inhibition. (C) Application of isoprenaline results in Rad phosphorylation by PKA, dissociation of a Rad fraction from the t-tubule membrane and relief of ICa,L inhibition. The inset shows Rad in relation to other RGK subfamily, Ras family, and Ras superfamily members.