In the healthy mammalian heart, the heart beat originates in the sinus node (SN). This specialised tissue of the heart is located at the junction of the right atrium with the superior caval vein and has unique structural and functional properties. Histologically, we have shown that in many mammalian species (mouse, rat, guinea-pig, rabbit, ferret and human) the SN tissue is embedded in a large network of connective tissue and contains cardiac cells that are smaller than working myocardial cells and not uniformly arranged. We have shown that this tissue can be delineated from its surrounding myocardium by some negative and positive immunohistochemical markers: ANP (atrial natriuretic peptide) and Cx43 (major cardiac gap junction channel protein) are negative markers whereas Cx45 (another gap junction channel protein) and NF-M (cytoskeletal protein) are positive markers. Over the last 10 years, using predominantly immunohistochemistry, but also Western blotting, quantitative PCR (qPCR) and in situ hybridisation on many mammalian species including human we have been studying expression and distribution of ion channel isoforms in the SN. We have shown that as compared to working myocardium: (1) HCN4 (the major isoform responsible for the pacemaker current, If) is more abundant in the rat and human SN; (2) Kir2.1 (responsible for the inward rectifier K+ current, IK,1) is less abundant in the mouse and human SN; (3) Nav1.5 (responsible for the cardiac Na+ current, INa) is less abundant in the rat and human SN; (4) Cav1.3 (responsible for the L-type Ca2+ current, IL,Ca) is more abundant in the rat and rabbit SN; (5) Kv1.4 and Kv4.3 (responsible for the transient K+ current, Ito) is present in the rabbit and human SN respectively; (6) Kv1.5 (responsible for the ultra-rapid delayed rectifier K+ current, IK,ur) is present in the rat and guinea-pig SN and (7) Kir3.1 and Kir3.4 (responsible for the acetylcholine-activated K+ current, IK,ACh) are present in the rat and human SN. In addition, we have shown that major Ca2+ handling proteins are differently expressed in e.g., the rabbit SN as compared to working myocardium; in particular RYR2 is less abundant in nodal cells. The unique ion channel expression profile of the SN can explain the unique electrophysiology of the SN.