Increased cardiac contractility during the fight-or-flight response is caused by β-adrenergic augmentation of Ca_V1.2 voltage-gated calcium channels^{, , –}. However, this augmentation persists in transgenic murine hearts expressing mutant Ca_V1.2 α_1C and β subunits that can no longer be phosphorylated by protein kinase A—an essential downstream mediator of β-adrenergic signalling—suggesting that non-channel factors are also required. Here we identify the mechanism by which β-adrenergic agonists stimulate voltage-gated calcium channels. We express α_1C or β_2B subunits conjugated to ascorbate peroxidase in mouse hearts, and use multiplexed quantitative proteomics^, to track hundreds of proteins in the proximity of Ca_V1.2. We observe that the calcium-channel inhibitor Rad^,, a monomeric G protein, is enriched in the Ca_V1.2 microenvironment but is depleted during β-adrenergic stimulation. Phosphorylation by protein kinase A of specific serine residues on Rad decreases its affinity for β subunits and relieves constitutive inhibition of Ca_V1.2, observed as an increase in channel open probability. Expression of Rad or its homologue Rem in HEK293T cells also imparts stimulation of Ca_V1.3 and Ca_V2.2 by protein kinase A, revealing an evolutionarily conserved mechanism that confers adrenergic modulation upon voltage-gated calcium channels.