More than 100 years after the discovery of the sinus node (SN) by Keith and Flack, the function and structure of the SN have not been completely established yet. The anatomic architecture of the SN has often been described as devoid of an organized structure; the origin of the sinus impulse is still a matter of debate, and a definite description of the long postulated internodal specialized tract conducting the impulse from the SN to the atrioventricular node (AVN) is still missing. In our previously published study, we proposed a morphologically ordered structure for the SN. As a confirmation of what was presented then, we have added the results of additional observations regarding the structural particularities of the SN. We investigated the morphology of the sinus node in the human hearts of healthy individuals using histochemical, immunohistochemical, optical, and electron microscopy (SEM, TEM). Our results confirmed that the SN presents a previously unseen highly organized architecture. 1. Introduction The first observation of the SN structure dates back to 1910, when Arthur Keith and Martin Flack introduced the world to the location of the sinus node (SN), observing that “we noted this structure, but attached no functional meaning to it” [1, 2]. A century after its discovery, the structure and function of the SN still remain a mystery which has yet to be unfolded. To the best of our knowledge, our previous published study on the architecture of the SN was the first to propose a model with a morphologically ordered structure [3]. First of all, the anatomic architecture of the SN has often been described as devoid of a definitive shape or an organized structure [4–10]. The results of the 3D reconstructions of the atrial elements [11–14] and the mathematical [15, 16] and ultrastructural models [17] of the SN are strongly divergent. The fact that the SN presents a different shape in humans, as compared to other mammals, complicates the task of creating a reliable model of this structure even more [6]. Second, the origin of the sinus impulse is still a matter of debate: what triggers it? Research in the fields of electrophysiology [18] and molecular biology [19–24] has pointed out that ion channels and intracellular Ca2 signalling are necessary for the proper setting of a pacemaker mechanism [25–38]. Brain-type Na channels have also recently been discovered, but their role is still unclear [39–41]. Sinus node automaticity is not fully understood, but it seems to arise from a dynamic balance between positive inward currents which favour depolarization
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