The contemporary view of the cardiac conduction system

Authors: David Sedmera 1,2;  František Vostárek 2
Authors‘ workplace: Anatomický ústav 1. LF UK, Praha 1;  Fyziologický ústav AV ČR, Praha 2
Published in: Čas. Lék. čes. 2017; 156: 417-421
Category: Review Articles


Cardiac conduction system was described in its complete form in homeotherm vertebrates 110 years ago. Despite this fact, many new findings concerning its specification and development that have an impact on its pacemaking and conducting function appeared in the past decade. Conduction system disorders are associated with arrhythmias, and some of which have a developmental origin. Evolutionary view on this area is particularly useful for better understanding of the atrioventricular canal remodelling.

Purkinje fibers, bundle branches, AV bundle, AV node, SA node


1. Sedmera D, Kurková D. Funkční a vývojový pohled na systém Purkyňových vláken. Časopis lékařů českých 2007; 146: 673–676.

2. Eliška O. Purkyňova vlákna převodního systému srdce – historie a současnost Purkyňových objevů. Časopis lékařů českých 2006; 145: 329–335.

3. Sedmera D, Pexieder T, Vuillemin M et al. Developmental patterning of the myocardium. Anat Rec 2000; 258: 319–337.

4. Christoffels VM, Hoogaars WM, Moorman AF. Patterning and development of the conduction system of the heart: origins of the conduction system in development. In: Rosenthal N, Harvey RP (eds.). Heart Development and Regeneration. Elsevier, London, 2010: 171–194.

5. Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 2005; 6: 826–835.

6. Christoffels VM, Mommersteeg MT, Trowe MO et al. Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res 2006; 98: 1555–1563.

7. Snarr BS, O’Neal JL, Chintalapudi MR et al. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res 2007; 101: 971–974.

8. Bressan M, Liu G, Mikawa T. Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science 2013; 340: 744–748.

9. Kirby ML, Gale TF, Stewart DE. Neural crest cells contribute to normal aorticopulmonary septation. Science 1983; 220: 1059–1061.

10. DiFrancesco D. Pacemaker mechanisms in cardiac tissue. Annu Rev Physiol 1993; 55: 455–472.

11. Mommersteeg MT, Brown NA, Prall OW et al. Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res 2007; 101: 902–909.

12. Mommersteeg MT, Hoogaars WM, Prall OW et al. Molecular pathway for the localized formation of the sinoatrial node. Circ Res 2007; 100: 354–362.

13. DiFrancesco D. The role of the funny current in pacemaker activity. Circ Res 2010; 106: 434–446.

14. Kolditz DP, Wijffels MC, Blom NA et al. Persistence of functional atrioventricular accessory pathways in postseptated embryonic avian hearts: implications for morphogenesis and functional maturation of the cardiac conduction system. Circulation 2007; 115: 17–26.

15. Suma K. Sunao Tawara: a father of modern cardiology. Pacing Clin Electrophysiol 2001; 24: 88–96.

16. Sedmera D, Gourdie RG. Why do we have Purkinje fibers deep in our heart? Physiol Res 2014; 63(Suppl. 1): S9–S18.

17. Blom NA, Gittenberger-de Groot AC, DeRuiter MC et al. Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity. Circulation 1999; 99: 800–806.

18. Hoogaars WM, Tessari A, Moorman AF et al. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res 2004; 62: 489–499.

19. Moorman AF, de Jong F, Denyn MM et al. Development of the cardiac conduction system. Circ Res 1998; 82: 629–644.

20. Gourdie RG. A map of the heart: gap junctions, connexin diversity and retroviral studies of conduction myocyte lineage. Clin Sci (Lond) 1995; 88: 257–262.

21. Bakker ML, Christoffels VM, Moorman AF. The cardiac pacemaker and conduction system develops from embryonic myocardium that retains its primitive phenotype. J Cardiovasc Pharmacol 2010; 56: 6–15.

22. Gourdie RG, Wei Y, Kim D et al. Endothelin-induced conversion of embryonic heart muscle cells into impulse-conducting Purkinje fibers. Proc Natl Acad Sci U S A 1998; 95: 6815–6818.

23. Chuck ET, Freeman DM, Watanabe M et al. Changing activation sequence in the embryonic chick heart. Implications for the development of the His-Purkinje system. Circ Res 1997; 81: 470–476.

24. Rečková M, Rosengarten C, deAlmeida A et al. Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 2003; 93: 77–85.

25. Sedmera D, Rečková M, Bigelow MR et al. Developmental transitions in electrical activation patterns in chick embryonic heart. Anat Rec A Discov Mol Cell Evol Biol 2004; 280: 1001–1009.

26. Karppinen S, Rapila R, Makikallio K et al. Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo. Acta Physiol (Oxf) 2014; 210: 369–380.

27. Hirota A, Kamino K, Komuro H et al. Early events in development of electrical activity and contraction in embryonic rat heart assessed by optical recording. J Physiol 1985; 369: 209–227.

28. Sedmera D, Wessels A, Trusk TC et al. Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture. Am J Physiol Heart Circ Physiol 2006; 291: H1646–H1652.

29. Leaf DE, Feig JE, Vasquez C et al. Connexin40 imparts conduction heterogeneity to atrial tissue. Circ Res 2008; 103: 1001–1008.

30. Ammirabile G, Tessari A, Pignataro V et al. Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium. Cardiovasc Res 2012; 93: 291–301.

31. Beneš J Jr, Ammirabil G, Šanková B et al. The role of connexin40 in developing atrial conduction. FEBS Lett 2014; 588: 1465–1469.

32. Liu J, Bressan M, Hassel D et al. A dual role for ErbB2 signaling in cardiac trabeculation. Development 2010; 137: 3867–3875.

33. Gourdie RG, Harris BS, Bond J et al. Development of the cardiac pacemaking and conduction system. Birth Defects Res C Embryo Today 2003; 69: 46–57.

34. Takebayashi-Suzuki K, Yanagisawa M, Gourdie RG et al. In vivo induction of cardiac Purkinje fiber differentiation by coexpression of preproendothelin-1 and endothelin converting enzyme-1. Development 2000; 127: 3523–3532.

35. Sedmera D, Harris BS, Grant E et al. Cardiac expression patterns of endothelin-converting enzyme (ECE): implications for conduction system development. Dev Dyn 2008; 237: 1746–1753.

36. Jay PY, Harri BS, Maguire CT et al. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 2004; 113(8): 1130–1137.

37. Jerome LA, Papaioannou VE. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 2001; 27(3): 286–291.

38. Moskowitz IP, Pizard A, Patel VV et al. The T-box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development 2004; 131: 4107–4116.

39. Hoogaars WM, Engel A, Brons JF et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev 2007; 21: 1098–1112.

40. Aanhaanen WT, Brons JF, Dominguez JN et al. The Tbx2+ primary myocardium of the atrioventricular canal forms the atrioventricular node and the base of the left ventricle. Circ Res 2009; 104: 1267–1274.

41. Zhang SS, Kim KH, Rosen A et al. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A 2011; 108: 13576–13581.

42. Frank DU, Carter KL, Thomas KR et al. Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis. Proc Natl Acad Sci U S A 2012; 109: E154–E163.

43. Šanková B, Machálek J, Sedmera D. Effects of mechanical loading on early conduction system differentiation in the chick. Am J Physiol Heart Circ Physiol 2010; 298: H1571–H1576.

44. Hall CE, Hurtado R, Hewett KW et al. Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart. Development 2004; 131: 581–592.

45. Naňka O, Křížová P, Fikrle M et al. Abnormal myocardial and coronary vasculature development in experimental hypoxia. Anat Rec (Hoboken) 2008; 291: 1187–1199.

46. Kolditz DP, Wijffels MC, Blom NA et al. Epicardium-derived cells in development of annulus fibrosis and persistence of accessory pathways. Circulation 2008; 117: 1508–1517.

47. Gurjarpadhye A, Hewett KW, Justus C et al. Cardiac neural crest ablation inhibits compaction and electrical function of conduction system bundles. Am J Physiol Heart Circ Physiol 2007; 292: H1291–H1300.

48. Buyon JP, Clancy RM. Neonatal lupus: review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus. Autoimmunity 2003; 36: 41–50.

49. Valderrabano M, Chen F, Dave AS et al. Atrioventricular ring reentry in embryonic mouse hearts. Circulation 2006. 114: 543–549.

50. Sedmera D, Kočková R, Vostárek F et al. Arrhythmias in the developing heart. Acta Physiol (Oxf) 2015; 213: 303–320.

51. Braunwald E, Zipes DP, Libbt P. Heart Disease: A Textbook of Cardiovascular Medicine (6th ed.). Saunders, Philadelphia, 2001: 2281.

52. Jongbloed MR, Schalij MJ, Poelmann RE et al. Embryonic conduction tissue: a spatial correlation with adult arrhythmogenic areas. J Cardiovasc Electrophysiol 2004; 15: 349–355.

53. Gonzalez MD, Contreras LJ, Jongbloed MR et al. Left atrial tachycardia originating from the mitral annulus-aorta junction. Circulation 2004; 110: 3187–3192.

54. Liang X, Wang G, Lin L et al. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res 2013; 113: 399–407.

55. Ye W, Wang J, Song Y et al. A common Shox2–Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node. Development 2015; 142(14): 2521–2532.

56. Ammirabile G, Tessari A, Pignataro V et al. Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium. Cardiovasc Res 2012; 93: 291–301.

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