New concepts in understanding and modulating atrial repolarisation in patients with atrial fibrillation
- 67 Downloads
Atrial fibrillation is the most frequent cardiac arrhythmia in clinical practice. Although much has been learned, the underlying mechanisms are incompletely understood. Clinically used antiarrhythmic drugs are limited in their efficacy to terminate atrial fibrillation or to maintain sinus rhythm and were associated with substantial toxicity including life-threatening ventricular arrhythmias. Novel therapeutic approaches suggest targeting of atrium-selective ion channels and pathology-specific alterations in atrial repolarisation and arrhythmogenesis as promising drug targets for patients with atrial fibrillation. This article focuses on novel aspects of altered atrial repolarisation and discusses atrium-selective (IKur, IK,ACh) and pathology-specific (IK,ACh) ion channels as potential targets for safe and effective treatment of atrial fibrillation.
KeywordsAtrial fibrillation Remodeling Atrium-selective targets IKur IK,ACh
The author’s research is supported by the German Federal Ministry of Education and Research (BMBF) through the Atrial Fibrillation Competence NETwork (AFNET, grant 01Gi0204) and by a grant of Fondation Leducq.
- 1.Wijffels, M. C., Kirchhof, C. J., Dorland, R., Power, J., & Allessie, M. A. (1997). Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: Roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation. Circulation, 96, 3710–3720.PubMedGoogle Scholar
- 8.Brundel, B. J. J. M., Van Gelder, I. C., Henning, R. H., Tieleman, R. G., Tuinenburg, A. E., Wietses, M., et al. (2001). Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation, 103, 684–690.PubMedGoogle Scholar
- 15.Dobrev, D., Graf, E., Wettwer, E., Himmel, H. M., Hála, O., Doerfel, C., et al. (2001). Molecular basis of down-regulation of G-protein-coupled inward rectifying K current (IK,ACh) in chronic human atrial fibrillation. Decrease in GIRK4 mRNA correlates with reduced IK,ACh and muscarinic receptor-mediated shortening of action potentials. Circulation, 104, 2551–2557.PubMedCrossRefGoogle Scholar
- 16.Voigt, N., Friedrich, A., Bock, M., Wettwer, E., Christ, T., Knaut, M., et al. (2007). Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK,ACh channels in patients with chronic atrial fibrillation. Cardiovascular Research, 74, 426–437.PubMedCrossRefGoogle Scholar
- 17.Ehrlich, J. R., Cha, T. J., Zhang, L., Chartier, D., Villeneuve, L., Hébert, T. E., et al. (2004). Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary veins myocardial sleeves and left atrium. Journal of Physiology(London), 557, 583–597.CrossRefGoogle Scholar
- 18.Voigt, N., Maguy, A., Yeh, Y. H., Qi, X., Ravens, U., Dobrev, D., et al. (2008). Changes in IK,ACh single channel activity with atrial tachycardia remodeling in canine atrial cardiomyocytes. Cardiovascular Research, 77, 35–43.Google Scholar