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Please use this identifier to cite or link to this item: http://hdl.handle.net/10373/253

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Title: Role of up-regulation of IK1 in action potential shortening associated with atrial fibrillation in humans
Authors: Zhang, Henggui
Garratt, Clifford J.
Zhu, Jiujiang
Holden, Arun V.
Affiliation: University of Abertay Dundee. School of Computing & Engineering Systems
Keywords: Human atrial fibrillation
Remodeling
Mathematical modeling
Issue Date: 2005
Publisher: Oxford University Press
Type: Journal Article
Refereed: peer-reviewed
Rights: Published version (c)Oxford University Press, available from DOI: 10.1016/j.cardiores.2005.01.020
Citation: Zhang, H., 2005. Role of up-regulation of IK1 in action potential shortening associated with atrial fibrillation in humans. Cardiovascular Research. 66(3): pp.493-502. [Online] Available from: DOI: 10.1016/j.cardiores.2005.01.020
Abstract: Objectives: Although previous studies in dogs have indicated a minimal role for changes in IK1 in the shortening of action potential duration (APD) associated with atrial fibrillation (AF), in humans, there is evidence for significant AF-induced up-regulation of this current. In this computer model study, we investigated the relative contributions of the remodeling of IK1, L-type calcium current, and other remodeled ionic channel currents to AF-induced APD reduction in human atrium. Methods: Two computer models of electrical activity of human atrial cell were modified by incorporating experimental data of AF-induced changes in human atrial ionic channel conductance and kinetics reported by Bosch et al. (ICaL, Ito, IK1, and INa) (AF-1) and Workman et al. (ICaL, Ito, and IK1) (AF-2). The roles and relative importance of individually remodeled ion channels in the APD reduction in human atrium were evaluated by the removal and exclusive methods, in which remodeling of specific currents was omitted, or considered in isolation, in the two models. Results: When tested together, previously reported AF-induced changes in sarcolemmal ion currents result in marked shortening of atrial APD90. With the AF-1 remodeled parameters, there is a 62% reduction in APD90 for the Nygren et al. model, and a 68% reduction for the Courtemanche et al. model, which are comparable to experimental results of 60% reduction seen in humans. When tested individually, AF-1-induced changes in ICaL, IK1, or Ito alone result in APD90 reduction of 20%, 64%, and –10%, respectively, for the Nygren et al. model, and 27%, 40%, and 11.6%, respectively, for the Courtemanche et al. model. With the AF-2 remodeled parameters, there is a 47% reduction in APD90 for the Nygren et al. model and a 49% reduction for the Courtemanche et al. model, which are also comparable to experimental results of 45% reduction. When tested individually, AF-2-induced changes in ICaL or IK1 alone result in APD90 reduction of 20% and 40%, respectively, for the Nygren et al. model, and 14% and 21%, respectively, for the Courtemanche et al. model. Conclusion: Previously reported changes in L-type Ca2+ current are insufficient to account for the observed reduction in atrial APD associated with persistent AF. Up-regulation of IK1 has a greater influence on atrial APD in the human model.
URI: http://hdl.handle.net/10373/253
ISSN: 0008-6363
Appears in Collections:Computing & Engineering Systems Collection

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