Skip to main content
SpringerLink
Log in

Current concepts of anatomy and electrophysiology of the sinus node

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

The sinoatrial node, or sinus node, of humans is the principal pacemaker of the heart. Over the last century, studies have unraveled the complex molecular architecture of the sinus node and the expression of unique ion channels within its specialized myocytes. Aim of this review is to describe the embriology, the anatomy, the histology and the electrophisiology of the sinus node.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Keith, A., & Flack, M. (1907). The form and nature of the muscular connections between the primary divisions of the vertebrate heart. Journal of Anatomy and Physiology, 41, 172–189.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Lewis, T. (1910). Galvanometric curves yielded by cardiac beats generated in various areas of the auricular musculature: the pacemaker of the heart. Heart, 2, 23–46.

    Google Scholar 

  3. Hoogaars, W. M., Engel, A., Brons, J. F., Verkerk, A. O., De Lange, F. J., Wong, L. Y., Bakker, M. L., et al. (2007). Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes and Development, 21, 1098–1112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hoogaars, W. M., Tessari, A., Moorman, A. F., De Boer, P. A., Hagoort, J., Soufan, A. T., Campione, M., et al. (2004). The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovascular Research, 62, 489–499.

    Article  CAS  PubMed  Google Scholar 

  5. Truex, R. C., Smythe, M. Q., & Taylor, M. J. (1967). Reconstruction of the human sinoatrial node. Anatomical Record, 159, 371–378.

    Article  CAS  PubMed  Google Scholar 

  6. Sanchez-Quintana, D., Cabrera, J. A., Farre, J., Climent, V., Anderson, R. H., & Ho, S. Y. (2007). Sinus node revisited in the era of electroanatomical mapping and catheter ablation. Heart, 91, 189–194.

    Article  Google Scholar 

  7. Lee, R. J., Kalman, J. M., Fitzpatrick, A. P., Epstein, L. M., Fisher, W. G., Olgin, J. E., Lesh, M. D., et al. (1995). Radiofrequency catheter modification of the sinus node for “inappropriate” sinus tachycardia. Circulation, 92, 2919–2928.

    Article  CAS  PubMed  Google Scholar 

  8. Anderson, K. R., Ho, S. Y., & Anderson, R. H. (1979). Location and vascular supply of sinus node in human heart. British Heart Journal, 41, 28–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hudson, R. E. B. (1960). The human pacemaker and its pathology. British Heart Journal, 22, 153–156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. James, T. N., Sherf, L., Fine, G., & Morales, A. R. (1966). Comparative ultrastructure of the sinus node in man and dog. Circulation, 34, 139–163.

    Article  CAS  PubMed  Google Scholar 

  11. Anderson, R. H., & Ho, S. Y. (1998). The architecture of the sinus node, the atrioventricular conduction axis, and the internal atrial myocardium. Journal of Cardiovascular Electrophysiology, 9, 1233–1248.

    Article  CAS  PubMed  Google Scholar 

  12. Chandler, N. J., Greener, I. D., Tellez, J. O., Inada, S., Musa, H., Molenaar, P., Difrancesco, D., et al. (2009). Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation, 119, 1562–1575.

    Article  PubMed  Google Scholar 

  13. Watanabe, E., Honjo, H., Anno, T., et al. (1995). Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model. American Journal of Physiology, 269, H1735–H1742.

    CAS  PubMed  Google Scholar 

  14. Anumonwo, J. M. B., Jalife, J., Zipes, D. P. (1995). Cellular and subcellular mechanisms of pacemaker activity initiation and synchronization in the heart. Cardiac electrophysiology: from cell to bedside. Philadelphia: Saunders.

  15. Fedorov, V. V., Schussler, R. B., Hemphill, M., et al. (2009). Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria. Circulation Research, 104, 915–923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Boyett, M. R., Inada, S., Yoo, S., Li, J., Liu, J., Tellez, J., Greener, I. D., et al. (2006). Connexins in the sinoatrial and atrioventricular nodes. Advances in Cardiology, 42, 175–197.

    Article  CAS  PubMed  Google Scholar 

  17. Fahrenback, J., Mejia-Alvarez, R., & Banach, K. (2007). The relevance of non-excitable cells for cardiac pacemaker function. Journal of Physiology, 585(2), 565–578.

    Article  Google Scholar 

  18. Alings, A. M., Abbas, R. F., & Bouman, L. N. (1993). Age-related changes in structure and relative collagen content of the human and feline sinoatrial node. A comparative study. European Heart Journal, 14, 1278–1288.

    Article  CAS  PubMed  Google Scholar 

  19. Demoulin, J. C., & Kulbertus, H. E. (1978). Histopathological correlates of sinoatrial disease. British Heart Journal, 40, 1384–1389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schuessler, R. B., Boineau, J. P., & Bromberg, B. I. (1996). Origin of the sinus impulse. Journal of Cardiovascular Electrophysiology, 7, 263–274.

    Article  CAS  PubMed  Google Scholar 

  21. Dilaveris, P. E., Farborn, P., Batchvarov, V., Ghuran, A., & Malik, M. (2001). Circadian behavior of P-wave duration, P-wave area and PR interval in healthy subjects. Annals of Noninvasive Electrocardiology, 6, 92–97.

    Article  CAS  PubMed  Google Scholar 

  22. Busquet, J., Fontan, F., Anderson, R. H., et al. (1984). The surgical significance of the atrial branches of the coronary arteries. International Journal of Cardiology, 6, 223–234.

    Article  CAS  PubMed  Google Scholar 

  23. Crick, S. J., Sheppard, M. N., Ho, S. Y., & Anderson, R. H. (1999). Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system. Journal of Anatomy, 195, 341–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Crick, S. J., Wharton, J., Sheppard, M. N., et al. (1994). Innervation of the human cardiac conduction system. A quantitative immunohistochemical and histochemical study. Circulation, 89, 1697–1708.

    Article  CAS  PubMed  Google Scholar 

  25. Uijtdehaage, S. H., & Thayer, J. F. (2000). Accentuated antagonism in the control of human heart rate. Clinical Autonomic Research, 10(3), 107–110.

    Article  CAS  PubMed  Google Scholar 

  26. Robinson, R. B., & Difrancesco, D. (2001). Sinoatrial node and impulse initiation. In P. Spooner & M. Rosen (Eds.), Foundations of cardiac arrhythmias: basic concepts and clinical approaches. New York: Marcel Dekker.

    Google Scholar 

  27. Vassalle, M., Yu, H., Cohen, I. S., Zipes, D. P., Jalife, J. (1995). Pacemaker channels and cardiac automaticity. Cardiac electrophysiology: from cell to bedside. Philadelphia: Saunders.

  28. Bleeker, W. K., MacKaay, A. J. C., Masson-Pevet, M., et al. (1980). Functional and morphologic organization of the rabbit sinus node. Circulation Research, 46, 11–22.

    Article  CAS  PubMed  Google Scholar 

  29. West, T. C. (1955). Ultramicroelectrode recording from the cardiac pacemaker. Journal of Pharmacology and Experimental Therapeutics, 115, 283–290.

    CAS  PubMed  Google Scholar 

  30. Bozler, E. (1943). The initation of impulses in cardiac muscle. American Journal of Physiology, 138, 273–282.

    Google Scholar 

  31. Maltsev, V. A., & Lakatta, E. G. (2008). Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function. Cardiovascular Research, 77, 274–284.

    Article  CAS  PubMed  Google Scholar 

  32. Maltsev, V. A., & Lakatta, E. G. (2007). Normal heart rhythm is initiated and regulated by an intracellular calcium clock within pacemaker cells. Heart, Lung & Circulation, 16(5), 335–348.

    Article  CAS  Google Scholar 

  33. Monfredi, O., Maltsev, V. A., & Lakatta, E. G. (2013). Modern concepts concerning the origin of the heartbeat. Physiology, 28, 74–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. DiFrancesco, D., & Borer, J. (2007). The funny current: cellular basis for the control of heart rate. Drugs, 67(Suppl 2), 15–24.

    Article  PubMed  Google Scholar 

  35. Shibata, E. F., & Giles, W. R. (1985). Ionic currents that generate the spontaneous diastolic depolarization in individual cardiac pacemaker cells. Proceedings of the National Academy of Sciences of the United States of America, 82, 7796–7800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Irisawa, H., Brown, H. F., & Giles, W. (1993). Cardiac pacemaking in the sinoatrial node. Physiological Reviews, 73, 197–227.

    CAS  PubMed  Google Scholar 

  37. Dobrzynski, H., Boyett, M. R., & Anderson, R. H. (2007). New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation, 115, 1921–1932.

    Article  PubMed  Google Scholar 

  38. DiFrancesco, D. (1981). A new interpretation of the pace-maker current in calf Purkinje fibres. Journal of Physiology, 314, 359–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Verkerk, A., Wilders, R., van Borren, M. M., et al. (2007). Pacemaker current (If) in the human sinoatrial node. European Heart Journal, 28, 2472–2478.

    Article  PubMed  Google Scholar 

  40. Nof, E., Luria, D., Brass, D., et al. (2007). Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation, 116, 463–470.

    Article  CAS  PubMed  Google Scholar 

  41. Bucchi, A., Barbuti, A., Baruscotti, M., & DiFrancesco, D. (2007). Heart rate reduction via selective ‘funny’ channel blockers. Current Opinion in Pharmacology, 7, 208–213.

    Article  CAS  PubMed  Google Scholar 

  42. Wainger, B. J., DeGennaro, M., Santoro, B., Siegelbaum, S. A., & Tibbs, G. R. (2001). Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature, 411, 805–810.

    Article  CAS  PubMed  Google Scholar 

  43. Noble, D., Denyer, J. C., Brown, H. F., & DiFrancesco, D. (1992). Reciprocal role of the inward currents ib, Na and if in controlling and stabilizing pacemaker frequency of rabbit sino-atrial node cells. Proceedings of the Royal Society of London B: Biological Sciences, 250, 199–207.

    Article  CAS  Google Scholar 

  44. Lombardi, F., Makikallio, T. H., Myerburg, R. J., & Huikuri, H. V. (2001). Sudden cardiac death: role of heart rate variability to identify patients at risk. Cardiovascular Research, 50, 210–217.

    Article  CAS  PubMed  Google Scholar 

  45. Kodama, I., Nikmaram, M. R., Boyett, M. R., Suzuki, R., Honjo, H., & Owen, J. M. (1997). Regional differences in the role of the Ca2+ and Na+ currents in pacemaker activity in the sinoatrial node. American Journal of Physiology, 272, H2793–H2806.

    CAS  PubMed  Google Scholar 

  46. Hagiwara, N., Irisawa, H., & Kameyama, M. (1988). Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells. Journal of Physiology, 395, 233–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bogdano, K. Y., Vinogradova, T. M., & Lakatta, E. G. (2001). Sinoatrial nodal cell ryanodine receptor and Na+-Ca2+ exchanger: molecular partners in pacemaker regulation. Circulation Research, 88, 1254–1258.

    Article  Google Scholar 

  48. Ju, Y. K., Chu, Y., Chaulet, H., Lai, D., Gervasio, O. L., Graham, R. M., Cannell, M. B., et al. (2007). Store-operated Ca2+ influx and expression of TRPC genes in mouse sinoatrial node. Circulation Research, 100, 1605–1614.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Oklahoma Health Sciences Center, Heart Rhythm Institute, Oklahoma City, OK, USA

    Cliona Murphy & Ralph Lazzara

Authors
  1. Cliona Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralph Lazzara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cliona Murphy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murphy, C., Lazzara, R. Current concepts of anatomy and electrophysiology of the sinus node. J Interv Card Electrophysiol 46, 9–18 (2016). https://doi.org/10.1007/s10840-016-0137-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-016-0137-2

Keywords

Search

Navigation