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A Mathematical Model of Electrotonic Interactions between Ventricular Myocytes and Fibroblasts

K. Andrew MacCannell ^*, Hojjat Bazzazi ^*, Lisa Chilton ^*, Yoshiyuki Shibukawa ^*, Robert B. Clark ^* and Wayne R. Giles ^* 

^* Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada

Correspondence: Address reprint requests to Dr. Wayne R. Giles, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada T2N 4N1. Tel.: 403-220-5607; Fax: 403-220-0448; E-mail: wgiles{at}ucalgary.ca.

Functional intercellular coupling has been demonstrated among networks of cardiac fibroblasts, as well as between fibroblasts and atrial or ventricular myocytes. In this study, the consequences of these interactions were examined by implementing the ten Tusscher model of the human ventricular action potential, and coupling it to our electrophysiological models for mammalian ventricular fibroblasts. Our simulations reveal significant electrophysiological consequences of coupling between 1 and 4 fibroblasts to a single ventricular myocyte. These include alterations in plateau height and/or action potential duration (APD) and changes in underlying ionic currents. Two series of simulations were carried out. First, fibroblasts were modeled as a spherical cell with a capacitance of 6.3 pF and an ohmic membrane resistance of 10.7 G. When these "passive" fibroblasts were coupled to a myocyte, they caused slight prolongation of APD with no changes in the plateau, threshold for firing, or rate of initial depolarization. In contrast, when the same myocyte-fibroblast complexes were modeled after addition of the time- and voltage-gated K⁺ currents that are expressed in fibroblasts, much more pronounced effects were observed: the plateau height of the action potential was reduced and the APD shortened significantly. In addition, each fibroblast exhibited significant electrotonic depolarizations in response to each myocyte action potential and the resting potential of the fibroblasts closely approximated the resting potential of the coupled ventricular myocyte.

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