The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The Gradient Model of the Rabbit Sinoatrial Node

  • Dobrzynski, H. (School of Biomedical Sciences, University of Leeds) ;
  • Lei, M. (University Laboratory of Physiology, University of Oxford) ;
  • Jones, S.A. (School of Biomedical Sciences, University of Leeds) ;
  • Lancaster, M.K. (School of Biomedical Sciences, University of Leeds) ;
  • Boyett, M.R. (School of Biomedical Sciences, University of Leeds)
  • Published : 2002.08.21
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Abstract

The sinoatrial (SA) node is a complex and inhomogeneous tissue in terms of cell morphology and electrical activity. There are two models of the cellular organisation of the sinoatrial node: the gradient and mosaic models. According to the gradient model there is a gradual transition in morphology and electrical properties of SA node cells from the centre to the periphery of the SA node. In the mosaic model, there is a variable mix of atrial and sinoatrial node cells from the centre to the periphery. This review focuses on the cellular organisation of the rabbit sinoatrial node in terms of the expression of connexin (Cx40, Cx43 and Cx45), L-type $Ca^{2+}$ channel and $Na^+-Ca^{2+}$ exchanger proteins. These immunocytochemical data, together with morphological and electrophysiological data, obtained from the intact sinoatrial node and isolated sinoatrial node cells support the gradient model of the cellular organisation of the SA node. The complex organisation of the sinoatrial node is important for the normal functioning of the sinoatrial node: (i) it allows the sinoatrial node to drive the surrounding hyperpolarized atrial muscle without being suppressed by it; (ii) it helps the pacemaker activity of the sinoatrial node continue under a wide range of physiological and pathophysiological conditions; (iii) it helps protect the sinoatrial node from reentrant arrhythmias.

Keywords

References

  1. Bleeker WK, Mackaay AJC, Masson-Pevet M, Bouman LN, Becker AE. Functional and morphological organization of the rabbit sinus node. Circ Res 46: 11－22, 1980 https://doi.org/10.1161/01.RES.46.1.11
  2. Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 47: 658－687, 2000 https://doi.org/10.1016/S0008-6363(00)00135-8
  3. Coppen SR, Kodama I, Boyett MR, Dobrzynski H, Takagishi Y, Honjo H, Yeh H-I, Severs NJ. Connexin45, a major connexin of the rabbit sinoatrial node, is co-expressed with connexin 43 in a restricted zone at the nodal-crista terminalis border. J Histochem Cytochem 47: 907－918, 1999 https://doi.org/10.1177/002215549904700708
  4. Denyer JC, Brown HF. Rabbit sino-atrial node cells: isolation and electrophysiological properties. J Physiol 428: 405－424, 1990 https://doi.org/10.1113/jphysiol.1990.sp018219
  5. Dobrzynski H. Immunocytochemical localisation of K$^+$channels in the sinoatrial node. University of Leeds. Ph.D. thesis, 2000
  6. Hata T, Noda T, Nishimura M, Watanabe Y. The role of Ca$^2+$ release from sarcoplasmic reticulum in the regulation of sinoatrial node automaticity. Heart Vessels 11: 234－241, 1996 https://doi.org/10.1007/BF01746203
  7. Honjo H, Boyett MR, Coppen SR, Takagishi Y, OpThof T, Severs NJ, Kodama I. Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size. Cardiovasc Res 53: 89－96, 2002 https://doi.org/10.1016/S0008-6363(01)00421-7
  8. Honjo H, Boyett MR, Kodama I, Toyama J. Correlation between electrical activity and the size of rabbit sinoatrial node cells. J Physiol 496: 795－808, 1996 https://doi.org/10.1113/jphysiol.1996.sp021728
  9. Joyner RW, Van Capelle FJL. Propagation through electrically coupled cells: how a small SA node drives a large atrium. Biophys J 50: 1157－1164, 1986 https://doi.org/10.1016/S0006-3495(86)83559-7
  10. Kodama I, Boyett MR. Regional differences in the electrical activity of the rabbit sinus node. Pflügers Arch 404: 214－226, 1985 https://doi.org/10.1007/BF00581242
  11. Musa H, Lei M, Honjo H, Jones SA, Dobrzynski H, Takagishi Y, Henderson Z, Kodama I, Boyett MR. Heterogeneous expression of Ca$^2+$ handling proteins in sinoatrial node. J Histochem Cytochem 50: 311－324, 2001
  12. OpThof T. The mammalian sinoatrial node. Cardiovasc Drugs Therapy 1: 573－597, 1988 https://doi.org/10.1007/BF02125744
  13. OpThof T. Gap junctions in the sinoatrial node: immunohistochemical localization and correlation with activation patterns. J Cardiovasc Electrophysiol 5: 138－143, 1994 https://doi.org/10.1111/j.1540-8167.1994.tb01153.x
  14. OpThof T, De Jonge B, Mackaay AJC, Bleeker WK, Masson-Pevet M, Jongsma HJ, Bouman LN. Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. J Mol Cell Cardiol 17: 549－564, 1985 https://doi.org/10.1016/S0022-2828(85)80024-9
  15. Rigg L, Terra DA. Possible role of calcium release from the sarcoplasmic reticulum in pacemaking in guinea-pig sino-atrial node. Exp Physiol 81: 877－880, 1996 https://doi.org/10.1113/expphysiol.1996.sp003983
  16. Severs NJ. The cardiac gap junctions and intercalated disc. Int J Cardiol 26: 137－173, 1990 https://doi.org/10.1016/0167-5273(90)90030-9
  17. Ten Velde I, De Jonge B, Verheijck EE, Van Kempen MJA, Analbers L, Gros D, Jongsma HJ. 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, 1995 https://doi.org/10.1161/01.RES.76.5.802
  18. Verheijck EE. Pacemaker currents in the sino-atrial node. University of Amsterdam. Ph.D. thesis, 1994
  19. Verheijck EE, Wessels A, Van Ginneken ACG, Bourier J, Markman MWM, Vermeulen JLM, De Bakker JMT, Lamers WH, OpThof T, Bouman LN. Distribution of atrial and nodal cells within rabbit sinoatrial node. Models of sinoatrial transition. Circulation 97: 1623－1631, 1998 https://doi.org/10.1161/01.CIR.97.16.1623
  20. Verheule S, Van Kempen MJA, Postma S, Rook MB, Jongsma HJ. Gap Junctions in the rabbit sinoatrial node. Am J Physiol 280: H2103－H2115, 2001
  21. Wu J, Schuessler RB, Rodefeld MD, Saffitz JE, Boineau JP. Morphological and membrane characteristics of spider and spindle cells isolated from rabbit sinus node. Am J Physiol 280: H1232－H1240, 2001
  22. Yamamoto M, Honjo H, Niwa R, Kodama I. Low frequency extracellular potentials recorded from the sinoatrial node. Cardiovas Res 39: 360－372, 1998 https://doi.org/10.1016/S0008-6363(98)00091-1
  23. Zhang H, Holden AV, Boyett MR. A gradient model of the intact SA node-initiation and propagation of pacemaker activity. Circulation 103: 584－588, 2001 https://doi.org/10.1161/01.CIR.103.4.584
  24. Zhang H, Holden AV, Kodama I, Honjo H, Lei M, Varghese T, Boyett MR. Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node. Am J Physiol 279: H397－H421, 2000