Figure 2.

Evidence of several pacemaker clusters in canine and human SANs. Figures are modified from Lou [50] and Li [4]. (A) Evidence supporting existence of pacemaker clusters in the canine SAN. Three pacemaker clusters located at head, center and tail SAN were identified during autonomic stimulation. Similar to mouse and rabbit SANs, Iso and ACh shifted the leading pacemaker from the center cluster (blue dots in a light blue area) into superior (red dots in a light red area, Iso) and inferior (white dots in a gray area, ACh) clusters. The figure summarizes four studies that optically located the leading pacemaker in the canine SAN [42,43,44,51]. Immunofluorescent detection showed various Cx43 expression patterns in distinct intranodal clusters. Further evidence from electrophysiological characterization also supported the existence of pacemaker clusters located at head, center and tail SAN, which is consistent with the findings from the pacemaker shift. Three clusters showed different action potential duration (APD) and dominate frequency distribution measured during atrial pacing. (B) Evidence supporting existence of multiple pacemakers in the human SAN. Similar to the canine SAN, three pacemaker clusters were identified in the human SAN evidenced from pacemaker shift and dominant frequency distribution during atrial pacing. Adenosine (Ado) shifted the leading pacemaker outside the central SAN majorly into the superior cluster and rarely to the inferior cluster. Green *: sinus exit pathway.