Organization of beta-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes.

Autor: Shcherbakova OG; Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 95305, USA., Hurt CM, Xiang Y, Dell'Acqua ML, Zhang Q, Tsien RW, Kobilka BK
Jazyk: angličtina
Zdroj: The Journal of cell biology [J Cell Biol] 2007 Feb 12; Vol. 176 (4), pp. 521-33.
DOI: 10.1083/jcb.200604167
Abstrakt: The sympathetic nervous system regulates cardiac function through the activation of adrenergic receptors (ARs). beta(1) and beta(2)ARs 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 beta(1) and beta(2)ARs 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 beta(1)ARs are enriched within these zones, whereas beta(2)ARs 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 beta(1) and beta(2)ARs in vivo.
Databáze: MEDLINE