Modelling cardiac fibroblasts: interactions with myocytes and their impact on impulse propagation
Department of Biomedical Engineering, Duke University, 260 Hudson Hall, Box 90281, Durham, NC 27708, USA
Aims: Existence of myocyte–fibroblast coupling in the human heart is still a controversial question. This study aims at investigating in a biophysical model how much coupling would be necessary to perturb significantly the electrical propagation of the cardiac impulse.
Methods and results: A one-dimensional model representing a strand of myocytes covered by a layer of fibroblasts was formulated by reinterpreting the coupled myocyte–fibroblast system as a single unit and connecting these units using a monodomain approach. The myocyte membrane kinetics was described by the Bondarenko mouse cell model and the fibroblast response was based on an experimentally measured current–voltage curve and took into account the delayed activation of that current. Conduction and maximal upstroke velocities were reported for different fibroblast densities and myocyte–fibroblast coupling strengths during paced rhythm. A reduction in conduction and maximum upstroke velocities was observed for increasing coupling and fibroblast density, in agreement with cell culture experiments. This effect was because of an increase in the myocyte resting potential and of the fibroblasts acting as a current sink. At least 10 fibroblasts with capacitance 4.5 pF had to be connected to each myocyte with capacitance 153.4 pF to slow down the conduction by >10%.
Conclusion: Coupling with fibroblasts affects the myocyte resting potential and the impulse propagation, but microstructural changes and myocyte decoupling are needed to explain slow conduction in fibrotic tissue.
Key Words: Impulse propagation, Conduction velocity, Fibroblast, Myocyte–fibroblast coupling
* Corresponding author. Tel: +1 919 660 5162; fax: +1 919 684 4488. E-mail address: vincent.jacquemet{at}a3.epfl.ch
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. C. McSpadden, R. D. Kirkton, and N. Bursac Electrotonic loading of anisotropic cardiac monolayers by unexcitable cells depends on connexin type and expression level Am J Physiol Cell Physiol, August 1, 2009; 297(2): C339 - C351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xie, A. Garfinkel, J. N. Weiss, and Z. Qu Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H775 - H784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Jacquemet and C. S. Henriquez Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2040 - H2052. [Abstract] [Full Text] [PDF]
|
|