The Role of the Hyperpolarization-Activated Inward Current 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_f and 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 If may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions