From the Department of Physiology (E.E.V., A.C.G.v.G., J.B., L.N.B.), the
Department of Anatomy and Embryology (A.W., M.W.M.M., J.L.M.V., W.H.L.), and
the Department of Clinical and Experimental Cardiology (J.M.T.d.B., T.O.),
Academic Medical Center, University of Amsterdam, The Netherlands.
Correspondence to Dr E. Etienne Verheijck, Department of Physiology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, Netherlands. E-mail e.verheijck{at}amc.uva.nl
Background—In the sinoatrial node
(SAN) the course of the action potential gradually changes from the
primary pacemaker region toward the atrium. It is not known whether
this gradient results from different intrinsic characteristics of the
nodal cells, from an increasing electrotonic interaction with the
atrium, or from both. Therefore we have characterized the
immunohistochemical, morphological, and
electrophysiological correlates of this
functional gradient.
Methods and Results—The distribution of rabbit nodal myocytes in
the SAN has been studied by immunohistochemistry. After cell isolation,
the electrophysiological characteristics of
different nodal cell types were measured. (1) The staining pattern of a
neurofilament protein coincides with the
electrophysiologically mapped pacemaker
region in the SAN. (2) Enzymatic digestion of the SAN reveals three
morphologically different nodal cell types and one atrial type. Of each
nodal cell type, neurofilament-positive as well as
neurofilament-negative myocytes are found. Atrial cells are all
neurofilament-negative. (3) In contrast to previous findings, we
observed atrial cells in the very center of the SAN. The relative
number of atrial cells gradually increases from the central pacemaker
area toward the atrium. (4) Differences in
electrophysiological characteristics
between individual nodal cells are not associated with differences in
cell type.
Conclusions—(1) The expression of neurofilaments can be used to
delineate the nodal area in the intact SAN but is not sufficiently
sensitive for characterizing all individual isolated nodal cells. (2) A
fundamentally different organization of the SAN is presented:
The gradual increase in density of atrial cells from the dominant area
toward the crista terminalis in the SAN causes a gradual increase of
atrial electrotonic influence that may be an important cause of the
gradual transition of the nodal to the atrial type of action potential.
© 1998 American Heart Association, Inc.
Basic Science Reports
Distribution of Atrial and Nodal Cells Within the Rabbit Sinoatrial Node
Models of Sinoatrial Transition
Key Words: pacemakers • cells • electrophysiology • immunohistochemistry
This article has been cited by other articles:
 |
|
 |
|
  V. V. Fedorov, R. B. Schuessler, M. Hemphill, C. M. Ambrosi, R. Chang, A. S. Voloshina, K. Brown, W. J. Hucker, and I. R. Efimov Structural and Functional Evidence for Discrete Exit Pathways That Connect the Canine Sinoatrial Node and Atria Circ. Res., April 10, 2009; 104(7): 915 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fukuzaki, T. Sato, T. Miki, S. Seino, and H. Nakaya Role of sarcolemmal ATP-sensitive K+ channels in the regulation of sinoatrial node automaticity: an evaluation using Kir6.2-deficient mice J. Physiol., June 1, 2008; 586(11): 2767 - 2778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Du and R. D. Nathan Simulated ischemia enhances L-type calcium current in pacemaker cells isolated from the rabbit sinoatrial node Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2986 - H2994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baruscotti and R. B. Robinson Electrophysiology and pacemaker function of the developing sinoatrial node Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2613 - H2623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Verkerk, R. Wilders, M. M.G.J. van Borren, R. J.G. Peters, E. Broekhuis, K. Lam, R. Coronel, J. M.T. de Bakker, and H. L. Tan Pacemaker current (If) in the human sinoatrial node Eur. Heart J., October 2, 2007; 28(20): 2472 - 2478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Lyashkov, M. Juhaszova, H. Dobrzynski, T. M. Vinogradova, V. A. Maltsev, O. Juhasz, H. A. Spurgeon, S. J. Sollott, and E. G. Lakatta Calcium Cycling Protein Density and Functional Importance to Automaticity of Isolated Sinoatrial Nodal Cells Are Independent of Cell Size Circ. Res., June 22, 2007; 100(12): 1723 - 1731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lei, H. Zhang, A. A. Grace, and C. L.-H. Huang SCN5A and sinoatrial node pacemaker function Cardiovasc Res, June 1, 2007; 74(3): 356 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, H. Dobrzynski, J. Yanni, M. R. Boyett, and M. Lei Organisation of the mouse sinoatrial node: structure and expression of HCN channels Cardiovasc Res, March 1, 2007; 73(4): 729 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. V. Fedorov, W. J. Hucker, H. Dobrzynski, L. V. Rosenshtraukh, and I. R. Efimov Postganglionic nerve stimulation induces temporal inhibition of excitability in rabbit sinoatrial node Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H612 - H623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dobrzynski, J. Li, J. Tellez, I.D. Greener, V.P. Nikolski, S.E. Wright, S.H. Parson, S.A. Jones, M.K. Lancaster, M. Yamamoto, et al. Computer Three-Dimensional Reconstruction of the Sinoatrial Node Circulation, February 22, 2005; 111(7): 846 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Miquerol, S. Meysen, M. Mangoni, P. Bois, H. V.M van Rijen, P. Abran, H. Jongsma, J. Nargeot, and D. Gros Architectural and functional asymmetry of the His-Purkinje system of the murine heart Cardiovasc Res, July 1, 2004; 63(1): 77 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Lakatta, V. A. Maltsev, K. Y. Bogdanov, M. D. Stern, and T. M. Vinogradova Cyclic Variation of Intracellular Calcium: A Critical Factor for Cardiac Pacemaker Cell Dominance Circ. Res., February 21, 2003; 92 (3): e45 - e50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rigg, P. A.D Mattick, B. M Heath, and D. A Terrar Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node Cardiovasc Res, February 1, 2003; 57(2): 497 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kurata, I. Hisatome, S. Imanishi, and T. Shibamoto Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2074 - H2101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O Verkerk, R. Wilders, J. G Zegers, M. M G J van Borren, J. H Ravesloot, and E E. Verheijck Ca2+-activated Cl- current in rabbit sinoatrial node cells J. Physiol., April 1, 2002; 540(1): 105 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Musa, M. Lei, H. Honjo, S. A. Jones, H. Dobrzynski, M. K. Lancaster, Y. Takagishi, Z. Henderson, I. Kodama, and M. R. Boyett Heterogeneous Expression of Ca2+ Handling Proteins in Rabbit Sinoatrial Node J. Histochem. Cytochem., March 1, 2002; 50(3): 311 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Honjo, M. R Boyett, S. R Coppen, Y. Takagishi, T. Opthof, N. J Severs, and I. Kodama Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size Cardiovasc Res, January 1, 2002; 53(1): 89 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ono, H. Masumiya, A. Sakamoto, G. Christe, T. Shijuku, H. Tanaka, K. Shigenobu, and Y. Ozaki Electrophysiological analysis of the negative chronotropic effect of endothelin-1 in rabbit sinoatrial node cells J. Physiol., December 1, 2001; 537(2): 467 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Opthof Function and structure of the mouse sinus node: nothing you can see that isn't shown Cardiovasc Res, October 1, 2001; 52(1): 1 - 4. [Full Text] [PDF]
|
|
|
|
|
|
E.E. Verheijck, M. J.A. van Kempen, M. Veereschild, J. Lurvink, H. J. Jongsma, and L. N. Bouman Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution Cardiovasc Res, October 1, 2001; 52(1): 40 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Mangoni and J. Nargeot Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells Cardiovasc Res, October 1, 2001; 52(1): 51 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verheule, M. J. A. van Kempen, S. Postma, M. B. Rook, and H. J. Jongsma Gap junctions in the rabbit sinoatrial node Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2103 - H2115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, A. V. Holden, and M. R. Boyett Gradient Model Versus Mosaic Model of the Sinoatrial Node Circulation, January 30, 2001; 103(4): 584 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rigg, B. M Heath, Y. Cui, and D. A Terrar Localisation and functional significance of ryanodine receptors during {beta}-adrenoceptor stimulation in the guinea-pig sino-atrial node Cardiovasc Res, November 1, 2000; 48(2): 254 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.R. Boyett, H. Honjo, and I. Kodama The sinoatrial node, a heterogeneous pacemaker structure Cardiovasc Res, September 1, 2000; 47(4): 658 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, A. V. Holden, I. Kodama, H. Honjo, M. Lei, T. Varghese, and M. R. Boyett Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H397 - H421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lei, H. Honjo, I. Kodama, and M.R. Boyett Characterisation of the transient outward K+ current in rabbit sinoatrial node cells Cardiovasc Res, June 1, 2000; 46(3): 433 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Benvenuti, V. D. Aiello, and M. de L. Higuchi Different Cell Types Within the Sinoatrial Node Circulation, August 31, 1999; 100 (9): 1011 - 1015. [Full Text] [PDF]
|
|
|
|
|
|
E. E. Verheijck, A. C. G. van Ginneken, R. Wilders, and L. N. Bouman Contribution of L-type Ca2+ current to electrical activity in sinoatrial nodal myocytes of rabbits Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H1064 - H1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Moroni, L. Gorza, M. Beltrame, B. Gravante, T. Vaccari, M. E. Bianchi, C. Altomare, R. Longhi, C. Heurteaux, M. Vitadello, et al. Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current If J. Biol. Chem., July 27, 2001; 276(31): 29233 - 29241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Verheijck, R. Wilders, and L. N. Bouman Atrio-Sinus Interaction Demonstrated by Blockade of the Rapid Delayed Rectifier Current Circulation, February 19, 2002; 105(7): 880 - 885. [Abstract] [Full Text] [PDF]
|
|