The role of the hyperpolarization-activated inward current I_f in arrhythmogenesis : a computer model study

Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current I_ f is increased under pathological conditions. Recent experimental data indicate a possible contribution of I_ f to arrhythmogenesis. In this paper, the role of I_ f in action potential propagation in normal and in pathological tissue is investigated by means of computer simulations. The effect of diffuse fibrosis and gap junction remodeling is simulated by reducing cellular coupling nonuniformly. As expected, the conduction velocity decreases when cellular coupling is reduced. In the presence of I_ f the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of I_ fand is facilitated by cellular uncoupling. We conclude that an increased I_ f may facilitate propagation of the action potential. Hence, I_ f may prevent conduction slowing and block. Overexpression of I_ f may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions.