Activation of β-adrenergic receptors and consequent phosphorylation by cAMP-dependent protein kinase A (PKA) greatly increases the L-type Ca²⁺ current through Ca_V1.2 channels in isolated cardiac myocytes. A kinase-anchoring protein 15 (AKAP15) coimmunoprecipitates with Ca_V1.2 channels isolated from rat heart membrane extracts and transfected cells, and it colocalizes with Ca_V1.2 channels and PKA in the transverse tubules of isolated ventricular myocytes. Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac Ca_V1.2 channel via a leucine zipper-like motif. Disruption of PKA anchoring to Ca_V1.2 channels via AKAP15 using competing peptides markedly inhibits the β-adrenergic regulation of Ca_V1.2 channels via the PKA pathway in ventricular myocytes. These results identify a conserved leucine zipper motif in the C terminus of the Ca_V1 family of Ca²⁺ channels that directly anchors an AKAP15-PKA signaling complex to ensure rapid and efficient regulation of L-type Ca²⁺ currents in response to β-adrenergic stimulation and local increases in cAMP.