The sinoatrial node (SAN) is the natural pacemaker of the heart, producing the electrical impulse that initiates every heart beat. Its activity is tightly controlled by the autonomic nervous system, and by circulating and locally released factors. Neurohumoral regulation of heart rate plays a crucial role in the integration of vital functions and influences behavior and ability to respond to changing environmental conditions. At the cellular level, modulation of SAN activity occurs through intracellular signaling pathways involving cyclic nucleotides: cyclic AMP (cAMP) and cyclic GMP (cGMP). In this Review, dedicated to Professor Dario DiFrancesco and his accomplishements in the field of cardiac pacemaking, we summarize all findings on the role of cyclic nucleotides signaling in regulating the key actors of cardiac automatism, and we provide an up-to-date review on cAMP- and cGMP-phosphodiesterases (PDEs), compellingly involved in this modulation.

窦房结 (SAN) 是心脏的自然起搏器，产生启动每次心跳的电脉冲。它的活动受到自主神经系统以及循环和局部释放的因子的严格控制。心率的神经体液调节在重要功能的整合中起着至关重要的作用，并影响行为和对不断变化的环境条件作出反应的能力。在细胞水平上，SAN 活性的调节通过涉及环核苷酸的细胞内信号通路发生：环 AMP (cAMP) 和环 GMP (cGMP)。在这篇评论中，致力于 Dario DiFrancesco 教授及其在心脏起搏领域的成就，我们总结了有关环核苷酸信号传导在调节心脏自动症关键因素中的作用的所有发现，