Département de Pharmacologie et de Toxicologie, Faculté de Biologie et Médecine, Université de Lausanne, Lausanne, Switzerland.
Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1742-53. doi: 10.1152/ajpheart.00569.2011. Epub 2011 Aug 19.
The pleiotropic cyclic nucleotide cAMP is the primary second messenger responsible for autonomic regulation of cardiac inotropy, chronotropy, and lusitropy. Under conditions of prolonged catecholaminergic stimulation, cAMP also contributes to the induction of both cardiac myocyte hypertrophy and apoptosis. The formation of localized, multiprotein complexes that contain different combinations of cAMP effectors and regulatory enzymes provides the architectural infrastructure for the specialization of the cAMP signaling network. Scaffolds that bind protein kinase A are called "A-kinase anchoring proteins" (AKAPs). In this review, we discuss recent advances in our understanding of how PKA is compartmentalized within the cardiac myocyte by AKAPs and how AKAP complexes modulate cardiac function in both health and disease.
多效性环核苷酸 cAMP 是负责自主调节心肌变力性、变时性和变松弛性的主要第二信使。在儿茶酚胺刺激持续的情况下，cAMP 也有助于诱导心肌细胞肥大和凋亡。包含不同组合的 cAMP 效应物和调节酶的局部多蛋白复合物的形成，为 cAMP 信号网络的专业化提供了结构基础。结合蛋白激酶 A 的支架称为“蛋白激酶 A 锚定蛋白”（AKAP）。在这篇综述中，我们讨论了最近在理解 AKAP 如何将 PKA 分隔在心肌细胞内以及 AKAP 复合物如何在健康和疾病中调节心脏功能方面的进展。
