Abstract:
3\', 5\'-cyclic adenosine monophosphate (cAMP) mediates the effects of sympathetic stimulation on the rate and strength of cardiac contraction. Beyond this pivotal role, in cardiac myocytes cAMP also orchestrates a diverse array of reactions to various stimuli. To ensure specificity of response, the cAMP signaling pathway is intricately organized into multiple, spatially confined, subcellular domains, each governing a distinct cellular function. In this review, we describe the molecular components of the cAMP signalling pathway, how they organized are inside the intracellular space and how they achieve exquisite regulation of signalling within nanometer-size domains. We delineate the key experimental findings that lead to the current model of compartmentalised cAMP signaling and we offer an overview of our present understanding of how cAMP nanodomains are structured and regulated within cardiac myocytes. Furthermore, we discuss how compartmentalized cAMP signaling is affected in cardiac disease and consider the potential therapeutic opportunities arising from understanding such organization. By exploiting the nuances of compartmentalized cAMP signaling, novel and more effective therapeutic strategies for managing cardiac conditions may emerge. Finally, we highlight the unresolved questions and hurdles that must be addressed to translate these insights into interventions that may benefit patients.
摘要:
3\',5'-环磷酸腺苷(cAMP)介导交感神经刺激对心脏收缩速率和强度的影响。除了这个关键角色,在心肌细胞中,cAMP还协调对各种刺激的各种反应。为了确保反应的特异性,cAMP信号通路错综复杂地组织成多个,空间限制,亚细胞域,每个控制着不同的细胞功能。在这次审查中,我们描述了cAMP信号通路的分子成分,它们是如何组织在细胞内空间内,以及它们如何在纳米尺寸的域内实现对信号的精致调节。我们描述了导致当前分隔cAMP信号传导模型的关键实验发现,并概述了我们目前对cAMP纳米结构域如何在心肌细胞内结构化和调节的理解。此外,我们讨论了cAMP信号如何在心脏病中受到影响,并考虑了由于了解这种组织而产生的潜在治疗机会。通过利用分隔的cAMP信号的细微差别,可能会出现新的和更有效的治疗心脏病的治疗策略.最后,我们强调了未解决的问题和障碍,必须解决这些问题和障碍,才能将这些见解转化为可能使患者受益的干预措施.