What is the structure and physiology of the sinoatrial (SA) node?

Structure and Physiology of the Sinoatrial (SA) Node

Structural Organization

The sinoatrial node is a three-dimensional intramural structure composed of a heterogeneous collection of morphologically and electrically distinct cells, including specialized pacemaker cells, transitional cells, endothelial cells, fibroblasts, and extracellular scaffolding. 1

Anatomical Location and Dimensions

• The SA node is a single, elongated structure located at the junction of the superior vena cava intercaval region, bordering the crista terminalis 2
• The anatomic SA node structure measures approximately 20 mm in length 2
• It exists as an intramural fibrotic structure, meaning it is embedded within the atrial wall rather than sitting on the surface 2

Cellular Composition and Architecture

• The central portion of the sinus node houses the dominant pacemaking function and contains cells with longer action potentials and faster rates of phase 4 diastolic depolarization than other cardiac cells 1
• Specialized cardiomyocytes of the sinus node are surrounded by strands of connective tissue that electrically insulate the pacemaker cells from atrial myocardial tissue 1
• This structural insulation is essential for normal functioning as it protects pacemaker cells from the suppressive effects of hyperpolarization from adjacent myocytes 1
• The node demonstrates prominent cellular heterogeneity with distinct populations of cells throughout its structure 1

Electrical Insulation and Exit Pathways

• An insulating border separates the SA node from the hyperpolarizing influence of the surrounding myocardium 3
• Electrical activation exits through discrete sinoatrial conduction pathways (sinoatrial exit pathways or SEPs) rather than diffusely across the entire node 2, 3
• These exit sites may be distributed up to 50 mm along the crista terminalis, extending well beyond the 20-mm anatomic SA node structure itself 2

Physiological Function

Pacemaker Mechanism

• The SA node is characterized by a unique ion channel and connexin expression profile that results in chronotropic automaticity 1
• Pacemaker cells exhibit spontaneous phase 4 diastolic depolarization, allowing them to reach threshold and generate action potentials without external stimulation 1
• The central nodal cells have faster rates of phase 4 depolarization compared to peripheral nodal cells and other cardiac tissues 1

Pace-and-Drive Capacity

• The SA node must perform two critical functions: spontaneous pacing (generating rhythmic depolarizations) and driving (exciting the large, hyperpolarized surrounding atrial tissue) 3
• Despite accounting for only a small proportion of total heart mass, the SA node must produce a stimulus of sufficient strength to activate the entire downstream cardiac tissue 4
• The sinoatrial exit pathways create a transition zone of transmembrane voltage and ionic currents that enables successful propagation from the small SA node to the large atrium 3
• Some degree of electrical uncoupling within the SA node itself appears to be an essential design feature that allows the node to remain spontaneously active while coupled to quiescent atrial cells 5

Impulse Propagation Pattern

• SA node activation originates in intranodal pacemakers and is conducted to the atria through one or more discrete sinoatrial conduction pathways 2
• The leading pacemaker site location shifts based on the distribution of exit pathways, typically located 3-4 mm from SEP-free areas where hyperpolarizing influence is reduced 3
• Fiber direction influences which exit pathways preferentially activate the crista terminalis 3

Molecular and Genetic Basis

Ion Channel Expression

• Differences in ion channel expression underlie the electrophysiological behavior differences between cell types within the SA node 1
• Genome-wide association analyses have identified multiple loci in ion channel and channel-interacting proteins related to normal and abnormal resting heart rates 1
• The L-type calcium channels and sodium-calcium exchanger play critical roles in successful impulse generation and propagation 3

Age-Related Changes

• Collagen content of the heart increases with age, and this increased fibrosis correlates with slower heart rate and slower sinoatrial conduction times 1
• Heart rate variability decreases with age, though the underlying mechanisms are not well understood 1
• Fibrosis of the sinus node is associated with fibrosis in the atrioventricular node, suggesting a systemic degenerative process 1

Clinical Implications

Common Pitfall in Mapping

• Surface-only multielectrode mapping during clinical procedures may not define the true leading pacemaker sites in the intramural SA node but instead misinterpret epicardial or endocardial exit sites through sinoatrial conduction pathways as the primary pacemaker location 2
• The three-dimensional intramural nature and complexity of SA node pacemaker structure and conduction are underappreciated during clinical mapping and ablation procedures 2