卷:12 | |
A-Kinase Anchoring Proteins in Cardiac Myocytes and Their Roles in Regulating Calcium Cycling | |
Review | |
关键词: CHANNEL RYANODINE RECEPTOR; HEART-FAILURE; FAILING HUMAN; SIGNALING COMPLEXES; GENE DELIVERY; KNOCKOUT MICE; CA2+ RELEASE; TROPONIN-I; PHOSPHORYLATION; MAKAP; | |
DOI : 10.3390/cells12030436 | |
来源: SCIE |
【 摘 要 】
The rate of calcium cycling and calcium transient amplitude are critical determinants for the efficient contraction and relaxation of the heart. Calcium-handling proteins in the cardiac myocyte are altered in heart failure, and restoring the proper function of those proteins is an effective potential therapeutic strategy. The calcium-handling proteins or their regulators are phosphorylated by a cAMP-dependent kinase (PKA), and thereby their activity is regulated. A-Kinase Anchoring Proteins (AKAPs) play a seminal role in orchestrating PKA and cAMP regulators in calcium handling and contractile machinery. This cAMP/PKA orchestration is crucial for the increased force and rate of contraction and relaxation of the heart in response to fight-or-flight. Knockout models and the few available preclinical models proved that the efficient targeting of AKAPs offers potential therapies tailor-made for improving defective calcium cycling. In this review, we highlight important studies that identified AKAPs and their regulatory roles in cardiac myocyte calcium cycling in health and disease.
【 授权许可】