Emerging Signaling Regulation of Sinoatrial Node Dysfunction.

Abstract

The sinoatrial node (SAN), the natural pacemaker of the heart, isresponsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causesvarious arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the mostrecent progress in the signaling regulation of SND. Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), and diabetes. These discoveries provide novel insights into the underlyingmechanisms SND, advancing our understanding of its pathogenesis. SND can cause severe cardiac arrhythmias associated with syncope and an increased risk of sudden death. In addition toion channels, the SAN is susceptible to the influence ofvarious signalings including Hippo, AMP-activated protein kinase (AMPK), mechanical force, and natriuretic peptide receptors. New cellular and molecular mechanisms related to SND are also deciphered in systemic diseases such as HF and diabetes. Progress in these studies contributes to the development of potential therapeutics for SND.