The Role of the Hyperpolarization-Activated Inward Current Irm fin Arrhythmogenesis: A Computer Model Study

• Published in: IEEE transactions on biomedical engineering 2006-08, Vol.53 (8), p.1499-1511
• Main Authors: Kuijpers, N.H.L., Keldermann, R.H., Ten Eikelder, H.M.M., Arts, T., Hilbers, P.A.J.
• Format: Article
• Language: English
• Subjects: Atrial fibrillation; bidomain model; Biomedical engineering; Computational modeling; Computer simulation; Couplings; ectopic activity; fibrosis; gap junction remodeling; hyperpolarization-activated inward current; Myocardium; Pathology; Permeability; Veins
• ISSN: 0018-9294; 1558-2531
• DOI: 10.1109/TBME.2006.877801

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