The Sinoatrial Node Gap Junction Distribution and Impulse Propagation

  • Mark R. Boyett
  • Haruo Honjo
  • Henggui Zhang
  • Yoshiko Takagishi
  • Itsuo Kodama
Part of the Basic Science for the Cardiologist book series (BASC, volume 12)


The function of the sinoatrial (SA) node is to act as the heart’s pacemaker and for this the cells of the SA node have to be electrically connected both to one another and also the atrial cells surrounding them. This chapter is concerned with the electrical coupling between cells in and around the SA node – it is shown that this is special, perhaps in order for the SA node to carry out its normal function. This chapter is written to complement our recent review of the functional and morphological organisation of the SA node (Boyett et al., 2000).


Sinoatrial Node Atrial Cell Interatrial Septum Sick Sinus Syndrome Atrial Muscle 


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  1. Alings, A. M. W., Abbas, R. F.,de Jonge, B., & Bouman, L. N.(1990).Structure and function of the simian sinoatrial node(Macaca fascicularis). J. Mol. Cell. Cardiol. 22, 1453–1466.PubMedCrossRefGoogle Scholar
  2. Alings, A.M.W., & Bouman, L.N. (1993). Electrophysiology of the aging rabbit and cat sinoatrial node. Eur. Heart, J. 14, 1278–1288.Google Scholar
  3. Anumonwo, J. M. B., Wang, H.-Z., Trabka-Janik, E., Dunham, B., Veenstra, R. D., Dalmar, M., & Jalife, J. (1992). Gap junctional channels in adult mammalian sinus nodal cells. Immunolocalization and electrophysiology. Circ. Res. 71, 229–239.Google Scholar
  4. Bleeker, W. K., Mackaay, A. J. C., Masson-Pevet, M., Op’t Hof, T., Jongsma, H. J., & Bouman, L. N. (1982). Asymmetry of the sino-atrial conduction in the rabbit heart. J. Mol. Cell. Cardiol. 14, 633–643.PubMedCrossRefGoogle Scholar
  5. Bonke, F. I. M. (1973a). Passive electrical properties of atrial fibers of the rabbit heart. Pflügers Arch. 339, 1–15.PubMedCrossRefGoogle Scholar
  6. Bonke, F. I. M. (1973b). Electrotonic spread in the sinoatrial node of the rabbit heart. Pflügers Arch. 339, 17–23.PubMedCrossRefGoogle Scholar
  7. Bouman, L. N., Duivenvoorden, J. J., Bukauskas, F. F., & Jongsma, H. J. (1989). Anisotropy of electrotonus in the sinoatrial node of the rabbit heart. J. Mol. Cell. Cardiol. 21, 407–418.PubMedCrossRefGoogle Scholar
  8. Boyett, M. R., Holden, A. V., Zliang, H., Kodama, I., & Suzuki, R. (1995). Atrial modulation of sinoatrial pacemaker rate. Chaos, Solitons & Fractals 5, 425–438.CrossRefGoogle Scholar
  9. Boyett, M. R., Honjo, H., & Kodama, I. (2000). The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc. Res. 47, 658–687.Google Scholar
  10. Bukauskas, F. F., Gutman, A. M., Kisunas, K. J., & Veteikis, R. P. (1982). Electrical cell coupling in rabbit sinoatrial node and atrium. Experimental and theoretical evaluation. In Cardiac Rate and Rhythum, eds. Bouman, L. N. & Jongsma, H. J., pp. 195–214. Martinus Nijhoff Publishers, The Hague, Boston, London.CrossRefGoogle Scholar
  11. Cabo, C., Pertsov, A. M., Baxter, W. T., Davidenko, J. M., Gray, R. A., & Jalife, J. (1994). Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle. Circ. Res. 75, 1014–1028.Google Scholar
  12. Cai, D., Winslow, R. L., & Noble, D. (1994). Effects of gap junction conductance on dynamics of sinoatrial node cells: two cell and large scale networks. IEEE Trans. Biomed. Eng. 41, 217–231.PubMedCrossRefGoogle Scholar
  13. Coppen, S.R., Dupont, E, Rothery, S., & Severs, J.N. (1998). Connexin45 expression is preferentially associated with the ventricular conduction system in mouse and rat heart. Circ. Res. 82, 232–243.Google Scholar
  14. Coppen, S. R., Kodama, I., Boyett, M. R., Dobrzynski, H., Takagishi, Y., Honjo, H., Yeh, H.-I., & Severs, N. J. (1999). Connexin45, a major connexin of the rabbit sinoatrial node, is co-expressed with connexin43 in a restricted zone at the nodal-crista terminalis border. J. Histochem. Cytochem. 47, 907–918.PubMedCrossRefGoogle Scholar
  15. Davidenko, J. M. (2001). Spiral waves in the heart: experimental demonstration of a theory. In: Cardiac Electrophysiology: From Cell to Bedside. Edited by D. P. Zipes and J. Jalife. Philadelphia: W.B. Saunders Company, 478–488.Google Scholar
  16. Davis, L.M., Kanter, F.H., Beyer E.C., & Saffitz, J.E. (1994). Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction properties. J. Am. Coll. Cardiol. 24, 1124–1132.PubMedCrossRefGoogle Scholar
  17. Davis, L.M., Rodefeld, M.E., Green, K., Beyer, E.C., & Saffitz, J.E. (1995). Gap junction phenotypes of the human heart and conduction system. J. Cardiovasc. Electrophysiol. 6, 813–822.PubMedCrossRefGoogle Scholar
  18. Fast, V.G., & Kleber, A.G. (1997). Role of wavefront curvature in propagation of cardiac impulse. Cardiovasc. Res. 33, 258–271.Google Scholar
  19. Ferrer, M.I. (1973). The sick sinus syndrome. Circulation 47, 635–641.PubMedCrossRefGoogle Scholar
  20. Goodenough, D.A., Goliger, J.A., & Paul, D.L. (1996). Connexins, connexons and intercellular communication. Ann. Rev. Biochem. 77, 1156–1163.Google Scholar
  21. Gourdie, R.G., Severs, N.J., Green, C.R., Rothery, S., Germroth, P., & Thompson, R.P. (1993). The spatial distribution and relative abundance of gap junctional connexin40 and connexin43 correlate to functional properties of the cardiac atrioventricular conduction system. J. Cell. Sci. 105, 985–991.PubMedGoogle Scholar
  22. He, D.S., Jiang, J.X., Taffet, S.M., & Burt, J.M. (1999). Formation of heteromeric gap junction channels by connexins 40 and 43 in vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA 96, 6495–6500.PubMedCrossRefGoogle Scholar
  23. Honjo, H., Boyett, M.R., Coppen, S.R., Takagishi, Y., Opthof, T., Severs, N.J., & Kodama, I. (2002). Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size. Cardiovasc. Res. 53, 89–96.Google Scholar
  24. Jones, S.A., & Boyett, M.R. (2001). Ageing of the heart: a comparison of young and senescent guinea pigs. J. Physiol. 533P.Google Scholar
  25. Joyner, R. W., Kumar, R., Golod, D., Wilders, R., Jongsma, H. J., Verheijck, E. E., Bouman, L. N., Goolsby, W. N., & van Ginneken, A. (1998). Electrical interactions between a rabbit atrial cell and a nodal cell model. Am. J. Physiol. 274, H2152–H2162.PubMedGoogle Scholar
  26. Joyner, R. W. & van Capelle, F. J. L. (1986). Propagation through electrically coupled cells: how a small SA node drives a large atrium. Biophys. J. 50, 1157–1164.Google Scholar
  27. Kirchhof, C. J. H. J. & Allessie, M. A. (1992). Sinus node automaticity during atrial fibrillation in isolated rabbit hearts. Circulation 86, 263–271PubMedCrossRefGoogle Scholar
  28. Kirchhof, C. J. H. J., Bonke, F. I. M., Allessie, M. A., & Lammers, W. J. E. P.(1987). The influence of the atrial myocardium on impulse formation in the rabbit sinus node. Pflügers Arch. 410, 198–203.PubMedCrossRefGoogle Scholar
  29. Kodama, I. & Boyett, M. R. (1985). Regional differences in the electrical activity of the rabbit sinus node. Pflügers Arch. 404, 214–226.PubMedCrossRefGoogle Scholar
  30. Kodama, I., Boyett, M. R., Suzuki, R., Honjo, H., & Toyama, J. (1996). Regional differences in the response of the isolated sinoatrial node of the rabbit to vagal stimulation. J. Physiol. 495, 785–801PubMedGoogle Scholar
  31. Kwong, K.F., Schuessler, R.B., Green, K.G., Laing, J.G., Beyer, E.C., Boineau, J.P., & Saffitz, J.E. (1998). Differential expression of gap junction proteins in the canine sinus node. Circ. Res. 82, 604–612.Google Scholar
  32. Masson-Pévet, M. A., Bleeker, W. K., & Gros, D. (1979). The plasma membrane of leading pacemaker cells in the rabbit sinus node: A quantitative ultrastructural analysis. Circ. Res. 45, 621–629.Google Scholar
  33. Michaels, D. C., Matyas, E. P., & Jalife, J. (1987). Mechanisms of sinoatrial pacemaker synchronization: a new hypothesis. Circ. Res. 61, 704–714.Google Scholar
  34. Oosthoek, P. W., Viragh, S., Mayen, A. E. M., van Kempen, M. J. A., Lamers, W. H., & Moorman, A. F. M. (1993). Immunohistochemical delineation of the conduction system. I: the sinoatrial node. Circ. Res. 73, 473–481.Google Scholar
  35. Opthof, T., de Jonge, B., Jongsma, H. J., & Bouman, L. N. (1987). Functional morphology of the pig sinoatrial node. J. Mol. Cell. Cardiol. 19, 1221–1236.PubMedCrossRefGoogle Scholar
  36. Opthof, T., de Jonge, B., Mackaay, A. J. C., Bleeker, W. K., Masson-Pevet, M., Jongsma, H. J., & Bouman, L. N. (1985). Functional anmorphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. J. Mol. Cell. Cardiol. 17, 549–564.PubMedCrossRefGoogle Scholar
  37. Opthof, T., de Jonge, B., Masson-Pevet, M., Jongsma, H. J., & Bouman, L. N. (1986). Functional and morphological organization of the cat sinoatrial node. J. Mol. Cell. Cardiol. 18, 1015–1031.PubMedCrossRefGoogle Scholar
  38. Saffitz, J. E., Green, K. G., & Schuessler, R. B. (1997). Structural determinants of slow conduction in the canine sinus node. J. Cardiovasc. Electrophysiol. 8, 738–744.PubMedCrossRefGoogle Scholar
  39. Severs, N.J. (1990). The cardiac gap junctions and intercalated disc. Int. J. Cardiol. 26, 137–173.Google Scholar
  40. Severs, N.J., Rothery, S, Dupont, E., Coppen, S.R., Yeh, H.-I., Ko, Y.-S., Matsushita, T., Kaba, R., & Halliday, D. (2001) Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system. Micros. Res. Tech. 52, 301–322.Google Scholar
  41. Seyama, I. (1976). Characteristics of the rectifying properties of the sinoatrial node cell of the rabbit. J. Physiol. 255, 379–397.PubMedGoogle Scholar
  42. ten Velde, I., de Jonge, B., Verheijck, E.E., van Kempen, M.J.A., Analbers, L., Gros, D., & Jongsma, H.J. (1995). Spatial distribution of connexin43, the major cardiac gap junction protein, visualizes the cellular network for impulse propagation from sinoatrial node to atrium. Circ. Res. 76, 802–811.PubMedCrossRefGoogle Scholar
  43. Toyama, J., Boyett, M. R., Watanabe, E.-I., Honjo, H., Anno, T., & Kodama, I. (1995). Computer simulation of the electrotonic modulation of pacemaker activity in the sinoatrial node by atrial muscle. J. Electrocardiol. 28 (supplement), 212–215.PubMedCrossRefGoogle Scholar
  44. Trabka-Janik, E., Coombs, W., Lemanski, L.F., Delmar, M., & Jalife, J. (1994). Immunohistochemical localization of gap junction protein channels in hamster sinoatrial node in correlation with electrophysiological mapping of the pacemaker region. Circ. Res. 71, 229–239.Google Scholar
  45. Valiunas, V., Weingart, R., & Brink, P.R. (2000). Formation of heterotypic gap junction channels by connexins 40 and 43. Circ. Res. 86, e42-e49.Google Scholar
  46. van Kempen, M.J.A., Fromaget, C., Gros, D., Moorman, A.F.M., & Lamers, W.H. (1991). Spatial distbution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart. Circ. Res. 68,1638–1651.Google Scholar
  47. Verheijck, E. E., van Kempen, M. J., Veereschild, M., Lurvink, J., Jongsma, H. J., & Bouman, L. N. (2001). Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution. Cardiovasc. Res. 52, 40–50.Google Scholar
  48. Verheijck, E. E., Wilders, R., Joyner, R. W., Golod, D., Kumar, R.,Jongsma, H. J.,Bouman,L. N., & van Ginneken, A. C. G. (1998). Pacemaker synchronization of electrically coupled rabbit sinoatrial node cells. J. Gen. Physiol. 111, 95–112.PubMedCrossRefGoogle Scholar
  49. Verheule, S., van Kempen, M. J., Postma, S., Rook, M. B., & Jongsma, H. J. (2001). Gap junctions in the rabbit sinoatrial node. Am. J. Physiol. 280, H2103–H2115.Google Scholar
  50. Verheule, S., van Kempen, M. J., te Welscher, P. H., Kwak, B. R., & Jongsma, H. J. (1997). Characterization of gap junction channels in adult rabbit atrial and ventricular myocardium. Circ. Res. 80, 673–681.Google Scholar
  51. Watanabe, E.-L, Honjo, H., Anno, T., Boyett, M. R., Kodama, I., & Toyama, J. (1995a). Electrotonic modulation of pacemaking activity in the sinoatrial node by atrial muscle. Heart and Vessels Supplement 9, 182–183.Google Scholar
  52. Watanabe, E.-I., Honjo, H., Anno, T., Boyett, M. R., Kodama, I., & Toyama, J. (1995b). Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model. Am. J. Physiol. 269, H1735–H1742.PubMedGoogle Scholar
  53. Yamamoto, M., Honjo, H., Niwa, R., & Kodama, I. (1998). Low frequency extracellular potentials recorded from the sinoatrial node. Cardiovasc. Res. 39, 360–372.Google Scholar
  54. Zhang, H., Boyett, M.R., Holden, A.V., Honjo, H., & Kodama, I. (1998). A hypothesis to explain the decline of sinoatrial node function with age. J. Physiol. 511, 76P–77P.CrossRefGoogle Scholar
  55. Zhang, H., Dobrzynski, H., Kodama, I., Takagishi, Y., Holden, A. V., & Boyett, M. R. (2001). How does the sinoatrial node drive the atrium? J. Physiol. 536P.Google Scholar
  56. Zhang, H., Holden, A. V., Kodama, I., Honjo, H., Lei, M., Takagishi, Y., & Boyett, M. R. (1999). Hypothesis to explain the block zone protecting the sinoatrial node. Biophys. J. 76, A368.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Mark R. Boyett
    • 1
    • 2
  • Haruo Honjo
    • 1
    • 2
  • Henggui Zhang
    • 1
    • 2
  • Yoshiko Takagishi
    • 1
    • 2
  • Itsuo Kodama
    • 1
    • 2
  1. 1.Reseach Institute of Environmental MedicineNagoya UniversityNagoyaJapan
  2. 2.School of Biomedical SciencesUniversity of LeedsLeedsUK

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