The sinus node (SN) is the primary cardiac pacemaker where the action potential originates to propagate to the right atrium. The SN is a specialized, complex, and heterogeneous tissue. Since its discovery, a large amount of data on small mammals has accumulated, but little information is available on humans. The molecular basis of ionic currents has been established for rabbits and mice, but, the "molecular architecture" of the human SN has not been elucidated. More information is needed not only on ion currents but also on the molecular nature of ion channels and their distribution. The SN is also one of the areas with the highest density of parasympathetic innervation of the autonomic nervous system (ANS). SN neurotransmitters contribute to modulating heart rate variability (HRV), a complex signal that facilitates our body's adaptation to the multiple external stimuli we receive from our environment. The SN is a control center, and its structure possibly evolved with the development of life on Earth and changes during the growth of each individual. The HRV has been extensively studied, but we still need to elucidate the relationship between its characteristics and the structure of the SN in humans. Finally, the structure of SN can be affected by various pathologies such as SN dysfunction. Chagas disease, endemic in America, can affect the SN causing various conduction disorders. It is necessary to elucidate the mechanisms by which the structure of the SN is altered and the relationship between this alteration and the HRV characteristics or conduction disorders.

From an evolutionary point of view, the architecture of the SN could have become more complex in more evolved organisms, improving the species' chances of survival. In individuals, the structure of the SN may develop during growth, while aging or some genetic or acquired diseases may alter it, producing specific changes in the HRV or several conduction disorders. This Research Topic will discuss the molecular architecture of the sinus node in humans, from the cellular to the systemic level. We aim to analyze its structure concerning its function as a control system.

Articles in this collection will focus on the impact of the architecture of the human SN on patient healthcare and treatment. Articles on basic physiology must consider the implications of their conclusions on patients’ health. Basic physiology studies on other animal species are not acceptable unless they make evolutionary sense. Works addressing the systemic level should include considerations at the molecular level in the discussion of the results. HRV studies are acceptable as long as the authors relate their study to the SN architecture. Researchers are encouraged to submit Original Research articles relevant to this article collection that will cover topics such as:

- Structure of the human SN on a molecular and cellular scale (ionic currents, distribution of channels, receptors, neurotransmitters, cells, and tissues, etc.)

- Influence of SN receptors on HRV

- Variation of the SN architecture with age

- Molecular basis of SN aging

- Diseases that affect the architecture of the SN, such as Chagas disease or SN disease

- Competence of the sinoatrial node in congenital complete heart block

- Evolution of the SN architecture

- Biophysical models for the SN

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