Copyright © 2005, European Society of Cardiology
Role of up-regulation of IK1 in action potential shortening associated with atrial fibrillation in humans
aBiological Physics Group, School of Physics and Astronomy, The University of Manchester, P.O. Box 88, Manchester M60 1QD, UK
bManchester Heart Centre, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK
cSchool of Biomedical Science, The University of Leeds, Leeds LS2 9JT, UK
* Corresponding author. Tel.: +44 161 200 3966; fax: +44 161 200 3940. Email address: h.zhang-3{at}umist.ac.uk
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.
KEYWORDS Human atrial fibrillation; Remodeling; Mathematical modeling
Time for primary review 23 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Divakaran and D. L. Mann The Emerging Role of MicroRNAs in Cardiac Remodeling and Heart Failure Circ. Res., November 7, 2008; 103(10): 1072 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Saygili, O. R. Rana, E. Saygili, H. Reuter, K. Frank, R. H. G. Schwinger, J. Muller-Ehmsen, and C. Zobel Losartan prevents stretch-induced electrical remodeling in cultured atrial neonatal myocytes Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2898 - H2905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nattel, A. Maguy, S. Le Bouter, and Y.-H. Yeh Arrhythmogenic Ion-Channel Remodeling in the Heart: Heart Failure, Myocardial Infarction, and Atrial Fibrillation Physiol Rev, April 1, 2007; 87(2): 425 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C.M. Choisy, L. A. Arberry, J. C. Hancox, and A. F. James Increased Susceptibility to Atrial Tachyarrhythmia in Spontaneously Hypertensive Rat Hearts Hypertension, March 1, 2007; 49(3): 498 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Noujaim, S. V. Pandit, O. Berenfeld, K. Vikstrom, M. Cerrone, S. Mironov, M. Zugermayr, A. N. Lopatin, and J. Jalife Up-regulation of the inward rectifier K+ current (IK1) in the mouse heart accelerates and stabilizes rotors J. Physiol., January 1, 2007; 578(1): 315 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Seemann, C. Hoper, F. B Sachse, O. Dossel, A. V Holden, and H. Zhang Heterogeneous three-dimensional anatomical and electrophysiological model of human atria Phil Trans R Soc A, June 15, 2006; 364(1843): 1465 - 1481. [Abstract] [Full Text] [PDF]
|
|