Propagation of pacemaker activity

Spontaneous activity of specific regions (e.g., the Sinoatrial node, SAN) is essential for the normal activation sequence of the heart and also serve as a primary means of modulating cardiac rate by sympathetic tone and circulating catecholamines. The mechanisms of how a small SAN region can electrically drive a much larger atrium, or how a small ectopic focus can drive surrounding ventricular or atrial tissue are complex, and involve the membrane properties and electrical coupling within the SAN or focus region as well as the membrane properties, coupling conductance magnitudes and also regional distribution within the surrounding tissue. We review here studies over the past few decades in which mathematical models and experimental studies have been used to determine some of the design principles of successful propagation from a pacemaking focus. These principles can be briefly summarized as (1) central relative uncoupling to protect the spontaneously firing cells from too much electrotonic inhibition, (2) a transitional region in which the cell type and electrical coupling change from the central SAN region to the peripheral atrial region, and (3) a distributed anisotropy to facilitate focal activity.

[1]  M R Boyett,et al.  Connexin45, a Major Connexin of the Rabbit Sinoatrial Node, Is Co-expressed with Connexin43 in a Restricted Zone at the Nodal-Crista Terminalis Border , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  R. Kumar,et al.  Determinants of action potential initiation in isolated rabbit atrial and ventricular myocytes. , 1998, American journal of physiology. Heart and circulatory physiology.

[3]  H Honjo,et al.  Computer Three-Dimensional Reconstruction of the Sinoatrial Node , 2005, Circulation.

[4]  R. Kumar,et al.  Electrical interactions between a rabbit atrial cell and a nodal cell model. , 1998, American journal of physiology. Heart and circulatory physiology.

[5]  R. Dehaan,et al.  Electrotonic interactions between aggregates of chick embryo cardiac pacemaker cells. , 1986, The American journal of physiology.

[6]  G. W. Beeler,et al.  Reconstruction of the action potential of ventricular myocardial fibres , 1977, The Journal of physiology.

[7]  R Wilders,et al.  Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells. , 2000, American journal of physiology. Heart and circulatory physiology.

[8]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. , 1994, Circulation research.

[9]  A. George,et al.  Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). , 2003, The Journal of clinical investigation.

[10]  R. W. Joyner,et al.  Propagation through Electrically Coupled Cells: Effects of Regional Changes in Membrane Properties , 1983, Circulation research.

[11]  D. Noble,et al.  Effects of gap junction conductance on dynamics of sinoatrial node cells: two-cell and large-scale network models , 1994, IEEE Transactions on Biomedical Engineering.

[12]  J A BUCHANAN,et al.  Cardiac rate and rhythm. , 1949, Medical record.

[13]  Mary B. Wagner,et al.  Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity , 2000, Pflügers Archiv.

[14]  F. V. Van Capelle,et al.  Propagation through electrically coupled cells. How a small SA node drives a large atrium. , 1986, Biophysical journal.

[15]  R Wilders,et al.  Pacemaker activity of the rabbit sinoatrial node. A comparison of mathematical models. , 1991, Biophysical journal.

[16]  P. Eggena,et al.  Downregulation of vasopressin receptors in toad bladder. , 1986, The American journal of physiology.

[17]  A. Camm,et al.  Arrhythmias in heart failure , 2006, The International Journal of Cardiac Imaging.

[18]  R Wilders,et al.  Beating irregularity of single pacemaker cells isolated from the rabbit sinoatrial node. , 1993, Biophysical journal.

[19]  Ronald Wilders,et al.  Pacemaker Synchronization of Electrically Coupled Rabbit Sinoatrial Node Cells , 1998, The Journal of general physiology.

[20]  R Wilders,et al.  Action potential conduction between a ventricular cell model and an isolated ventricular cell. , 1996, Biophysical journal.

[21]  I. Efimov,et al.  Structure-function relationship in the AV junction. , 2004, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[22]  Itsuo Kodama,et al.  Regional differences in the electrical activity of the rabbit sinus node , 1985, Pflügers Archiv.

[23]  A. Kleber,et al.  Animal models of cardiac arrhythmias. , 1998, Cardiovascular research.

[24]  H. Jongsma,et al.  On the Ultrastructural Identification of Pacemaker Cell Types within the Sinus Node , 1982 .

[25]  Akinori Noma,et al.  Pacemaker Mechanisms of Rabbit Sinoatrial Node Cells , 1982 .

[26]  R Wilders,et al.  A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet. , 2000, American journal of physiology. Heart and circulatory physiology.

[27]  M. Courtemanche,et al.  Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. , 1998, The American journal of physiology.