| We present here the experimental data upon which these mathematical models have been developed; as well as the derivation of the mathematical properties of the cardiac fibroblast, and the development of the necessary mathematical paradigms which describe the myocyte-myocyte and myocyte-fibroblast electrotonic coupling. A rigorous mathematical formalism of the voltage- and time-dependent properties of the cardiac fibroblast has been developed. Using a previously-developed model of the human ventricular myocyte we have studied the effects of electromechanical coupling between cardiac fibroblasts and ventricular myocytes in detail, and have, in particular, studied the effects upon excitation and excitability, myocyte action potential duration, and the influence of the cardiac fibroblast upon signal propagation in a functional syncytium.; From experimental data collected from freshly-dissociated and cultured fibroblasts, we have been able to derive a system of differential equations which dictate the time- and voltage-dependent behaviour of the currents expressed in the cardiac fibroblast, and to extend that model into a functional coupling between the fibroblast and the surrounding myocytes. Using a previously derived model for the human ventricular myocyte, we developed the mathematical descriptors of the coupling between the myocyte and cardiac fibroblast to determine what effect the cardiac fibroblast could have upon the human myocyte.; Our simulations suggest that the fibroblast not only significantly alters the action potential waveform of the myocyte to which it is coupled, but it may have significant consequences for the contractility of the heart ventricle. In addition, the currents across the fibroblast membrane can significantly depress the myocyte action potential plateau, and slow propagation through a linear chain of myocytes. |
