The role of the hyperpolarization-activated inward current If 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 If is increased under pathological conditions. Recent experimental data indicate a possible contribution of If to arrhythmogenesis. In this paper, the role of If 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 If the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of If and is facilitated by cellular uncoupling. We conclude that an increased If may facilitate propagation of the action potential. Hence, If may prevent conduction slowing and block. Overexpression of If may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions.
Kuijpers
Nico H L
NH
Department of Biomedical Engineering, Technische Universiteit Eindhoven, The Netherlands. N.H.L.Kuijpers@tue.nl
Keldermann
Rikkert H
RH
ten Eikelder
Huub M M
HM
Arts
Theo
T
Hilbers
Peter A J
PA
D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D003198:Computer Simulation; D017629:Gap Junctions; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels; D008564:Membrane Potentials; D008954:Models, Biological; D008955:Models, Cardiovascular
D007473:Ion Channels