Conduction in bullfrog atrial strands: simulations of the role of disc and extracellular resistance.

A number of fundamental properties of intercellular conduction in simulated cylindrical strands of cardiac tissue are examined. The paper is based on recent biophysical information describing the transmembrane ionic currents in bullfrog atrial cells as well as anatomical data on the structures (gap junctions) responsible for the coupling between cells in that tissue. A mathematical model of the single bullfrog atrial cell based on suction microelectrode single-cell voltage clamp data is employed, as well as a modified version of the well-known model of Heppner and Plonsey, to characterized the resistive connections between adjacent cells in a cardiac strand. In addition, the simulated cellular strand is assumed to be encased in a cylindrical, resistive endothelial sheath, thus forming an idealized atrial trabeculum; the trabeculum is immersed in an extensive volume conductor. It is possible to simulate both uniform and discontinuous conduction in this atrial strand model by appropriately changing the resistance of the intercalated discs that occur at cell boundaries. The conduction velocity achieved in the normal or control case is within the range of conduction velocities that have been measured for bullfrog atrial trabeculae using optical methods. Extracellular resistance is shown to have a significant effect on both conduction velocity and the critical value of disc resistance at which discontinuous conduction first occurs. Since the atrial cell model employed in this study is based on experimental data and can accurately simulate the atrial action potential, the transmembrane ionic currents generated by the model are capable of providing detailed information concerning the mechanisms of intercellular current spread, particularly in the region of the intercalated disc.

[1]  W. Giles,et al.  A time- and voltage-dependent K+ current in single cardiac cells from bullfrog atrium , 1986, The Journal of general physiology.

[2]  M Delmar,et al.  Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle. , 1987, Circulation research.

[3]  J M Kootsey,et al.  Low conduction in cardiac muscle. Biophysical model. , 1973, Biophysical journal.

[4]  R. W. Joyner,et al.  Propagation through electrically coupled cells: two inhomogeneously coupled cardiac tissue layers. , 1984, The American journal of physiology.

[5]  W. Giles,et al.  Sodium current in single cells from bullfrog atrium: voltage dependence and ion transfer properties. , 1987, The Journal of physiology.

[6]  F A Roberge,et al.  Revised formulation of the Hodgkin-Huxley representation of the sodium current in cardiac cells. , 1987, Computers and biomedical research, an international journal.

[7]  B. Katzung,et al.  Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. , 1977, Biochimica et biophysica acta.

[8]  H. Fozzard,et al.  A cleft model for cardiac Purkinje strands. , 1981, Biophysical journal.

[9]  W. Giles,et al.  Ionic currents in single isolated bullfrog atrial cells , 1983, The Journal of general physiology.

[10]  R. Niedergerke,et al.  Structures of physiological interest in the frog heart ventricle. , 1972, Journal of cell science.

[11]  R Suzuki,et al.  Simulation analysis of excitation conduction in the heart: propagation of excitation in different tissues. , 1986, Journal of theoretical biology.

[12]  T Powell,et al.  Sodium current in single rat heart muscle cells. , 1981, The Journal of physiology.

[13]  F A Roberge,et al.  Reconstruction of Propagated Electrical Activity with a Two‐Dimensional Model of Anisotropic Heart Muscle , 1986, Circulation research.

[14]  E. Johnson,et al.  Fast sodium current in cardiac muscle. A quantitative description. , 1980, Biophysical journal.

[15]  R. Tsien,et al.  Excitable Tissues: The Heart , 1978 .

[16]  R. Weingart,et al.  Electric current flow in cell pairs isolated from adult rat hearts. , 1985, The Journal of physiology.

[17]  M. Lieberman,et al.  A note on the reactivation of the fast sodium current in spherical clusters of embryonic chick heart cells. , 1983, Biophysical journal.

[18]  J. Bigger,et al.  Effect of Lidocaine on the Early Inward Transient Current in Sheep Cardiac Purkinje Fibers , 1975, Circulation research.

[19]  John W. Clark,et al.  Extracellular potentials from skeletal muscle , 1987 .

[20]  M. Spach,et al.  Relating the Sodium Current and Conductance to the Shape of Transmembrane and Extracellular Potentials by Simulation: Effects of Propagation Boundaries , 1985, IEEE Transactions on Biomedical Engineering.

[21]  J. Clark,et al.  A model of slow conduction in bullfrog atrial trabeculae. , 1991, Mathematical biosciences.

[22]  R. Weingart Electrical properties of the nexal membrane studied in rat ventricular cell pairs. , 1986, The Journal of physiology.

[23]  N. Sperelakis,et al.  Gap junction uncoupling and discontinuous propagation in the heart. A comparison of experimental data with computer simulations. , 1988, Biophysical journal.

[24]  R. Tsien,et al.  Maximal Upstroke Velocity as an Index of Available Sodium Conductance: Comparison of Maximal Upstroke Velocity and Voltage Clamp Measurements of Sodium Current in Rabbit Purkinje Fibers , 1984, Circulation research.

[25]  T. Colatsky,et al.  Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres. , 1980, The Journal of physiology.

[26]  H. Komuro,et al.  Conduction pattern of excitation in the amphibian atrium assessed by multiple-site optical recording of action potentials. , 1986, The Japanese journal of physiology.

[27]  D. Noble,et al.  Reconstruction of the electrical activity of cardiac Purkinje fibres. , 1975, The Journal of physiology.

[28]  L. Barr,et al.  Propagation of Action Potentials and the Structure of the Nexus in Cardiac Muscle , 1965, The Journal of general physiology.

[29]  D. Geselowitz,et al.  The Discontinuous Nature of Propagation in Normal Canine Cardiac Muscle: Evidence for Recurrent Discontinuities of Intracellular Resistance that Affect the Membrane Currents , 1981, Circulation research.

[30]  D. Noble,et al.  The contribution of potassium accumulation to outward currents in frog atrium. , 1980, The Journal of physiology.

[31]  S. Weidmann,et al.  Cardiac resting and action potentials recorded with an intracellular electrode , 1951, The Journal of physiology.

[32]  J. Clark,et al.  A mathematical model of electrophysiological activity in a bullfrog atrial cell. , 1990, The American journal of physiology.

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

[34]  D Durrer,et al.  Computer Simulation of Arrhythmias in a Network of Coupled Excitable Elements , 1980, Circulation research.

[35]  L. Wilkins Comments on "Maximal upstroke velocity as an index of available sodium conductance: comparison of maximal upstroke velocity and voltage clamp measurements of sodium current in rabbit Purkinje fibers". , 1985, Circulation research.

[36]  R. W. Joyner,et al.  Simulated propagation of cardiac action potentials. , 1980, Biophysical journal.

[37]  S. Weidmann,et al.  The effect of the cardiac membrane potential on the rapid availability of the sodium‐carrying system , 1955, The Journal of physiology.

[38]  Michael D. Lesh,et al.  Cellular Uncoupling Can Unmask Dispersion of Action Potential Duration in Ventricular Myocardium A Computer Modeling Study , 1989, Circulation research.

[39]  G. Vassort,et al.  Ultrastructural changes in gap junctions associated with CO2 uncoupling in frog atrial fibres. , 1985, Journal of cell science.

[40]  M. Kameyama Electrical coupling between ventricular paired cells isolated from guinea‐pig heart. , 1983, The Journal of physiology.

[41]  D. Brody,et al.  Microelectrode Study of Delayed Conduction in the Canine Right Bundle Branch , 1968, Circulation research.

[42]  J. Spear,et al.  Effects of Cellular Uncoupling on Conduction in Anisotropic Canine Ventricular Myocardium , 1988, Circulation research.

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

[44]  Yoram Rudy,et al.  A model study of the effects of the discrete cellular structure on electrical propagation in cardiac tissue. , 1987 .

[45]  W. Giles,et al.  Active and passive electrical properties of single bullfrog atrial cells , 1981, The Journal of general physiology.

[46]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[47]  D. E. Goldman POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES , 1943, The Journal of general physiology.

[48]  P J Hunter,et al.  Analytical models of propagation in excitable cells. , 1975, Progress in biophysics and molecular biology.

[49]  D DiFrancesco,et al.  A model of cardiac electrical activity incorporating ionic pumps and concentration changes. , 1985, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[50]  E. Johnson,et al.  The differential effect of quinidine and pyrilamine on the myocardial action potential at various rates of stimulation. , 1957, The Journal of pharmacology and experimental therapeutics.

[51]  D. B. Heppner,et al.  Simulation of electrical interaction of cardiac cells. , 1970, Biophysical journal.

[52]  R. W. Joyner,et al.  Effects of the Discrete Pattern of Electrical Coupling on Propagation through an Electrical Syncytium , 1982, Circulation research.

[53]  S. Weidmann,et al.  Effects of calcium ions and local anaesthetics on electrical properties of Purkinje fibres , 1955, The Journal of physiology.

[54]  R. Barr,et al.  Propagation of excitation in idealized anisotropic two-dimensional tissue. , 1984, Biophysical journal.

[55]  S. Rush,et al.  A Practical Algorithm for Solving Dynamic Membrane Equations , 1978, IEEE Transactions on Biomedical Engineering.

[56]  Ronald W. Joyner,et al.  Simulation of Action Potential Propagation in an Inhomogeneous Sheet of Coupled Excitable Cells , 1975, Circulation research.

[57]  G. N. Lance,et al.  Numerical methods for high speed computers , 1960 .