Organization of β-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes

The sympathetic nervous system regulates cardiac function through the activation of adrenergic receptors (ARs). β₁ and β₂ARs are the primary sympathetic receptors in the heart and play different roles in regulating cardiac contractile function and remodeling in response to injury. In this study, we examine the targeting and trafficking of β₁ and β₂ARs at cardiac sympathetic synapses in vitro. Sympathetic neurons form functional synapses with neonatal cardiac myocytes in culture. The myocyte membrane develops into specialized zones that surround contacting axons and contain accumulations of the scaffold proteins SAP97 and AKAP79/150 but are deficient in caveolin-3. The β₁ARs are enriched within these zones, whereas β₂ARs are excluded from them after stimulation of neuronal activity. The results indicate that specialized signaling domains are organized in cardiac myocytes at sites of contact with sympathetic neurons and that these domains are likely to play a role in the subtype-specific regulation of cardiac function by β₁ and β₂ARs in vivo.