Recent research highlights the complex anatomy of the sinus node, the dual role of membrane and calcium clocks in automaticity, and molecular links to sinus node remodeling in aging and disease.
PURPOSE OF REVIEW: Sinus node disease (SND) is a common clinical condition and is the most common indication for permanent pacemaker implantation. This review aims to revisit the complex sinus node anatomy, the evolving understanding of its pacemaking mechanisms, the atrial myopathy in SND and sinus node remodeling. RECENT FINDINGS: Recent high-density noncontact mapping of the human sinus node showed multiple origins of sinus activation and exit sites with preferential pathways of conduction. Perhaps, a newly described discrete paranodal area containing a molecular mixture of nodal and atrial cells may account for this long recognized discrepancy between the anatomical and functional sinus node. The funny current (I(f)) driven 'membrane clock' is not solely responsible for sinus node automaticity, following recent recognition of the importance of the 'calcium clock'. Several molecular links to sinus node remodeling have recently been identified: loss of connexin-43 expression and down-regulation of I(ca,L) in aging; reduced I(f) and down-regulation of I(f) encoding HCN4 and HCN2 subunits in heart failure; and calcium clock malfunction with down-regulated HCN4, HCN2 and minK in atrial fibrillation. SUMMARY: Ongoing research with improved technology and techniques continues to unravel new understandings and challenges to the century old discovery of the anatomical sinus node.
Lau et al. (Tue,) conducted a review in Sinus node disease. Recent research highlights the complex anatomy of the sinus node, the dual role of membrane and calcium clocks in automaticity, and molecular links to sinus node remodeling in aging and disease.