The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The β₂adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca_v1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate–dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein–coupled receptor.