The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Human Atrial Action Potential and Ca 2+ Model: Sinus Rhythm and Chronic Atrial Fibrillation
Open accessAbstract
Rationale: Understanding atrial fibrillation (AF) requires integrated understanding of ionic currents and Ca 2+ transport in remodeled human atrium, but appropriate models are limited. Objective: To study AF, we developed a new human atrial action potential (AP) model, derived from atrial experimental results and our human ventricular myocyte model. Methods and Results: Atria versus ventricles have lower I K1 , resulting in more depolarized resting membrane potential (≈7 mV). We used higher I to,fast density in atrium, removed I to,slow , and included an atrial-specific I Kur . I NCX and I NaK densities were reduced in atrial versus ventricular myocytes according to experimental results. SERCA function was altered to reproduce human atrial myocyte Ca 2+ transients. To simulate chronic AF, we reduced I CaL , I to , I Kur and SERCA, and increased I K1 ,I Ks and I NCX . We also investigated the link between Kv1.5 channelopathy, [Ca 2+ ] i , and AF. The sinus rhythm model showed a typical human atrial AP morphology. Consistent with experiments, the model showed shorter APs and reduced AP duration shortening at increasing pacing frequencies in AF or when I CaL was partially blocked, suggesting a crucial role of Ca 2+ and Na + in this effect. This also explained blunted Ca 2+ transient and rate-adaptation of [Ca 2+ ] i and [Na + ] i in chronic AF. Moreover, increasing [Na + ] i and altered I NaK and I NCX causes rate-dependent atrial AP shortening. Blocking I Kur to mimic Kv1.5 loss-of-function increased [Ca 2+ ] i and caused early afterdepolarizations under adrenergic stress, as observed experimentally. Conclusions: Our study provides a novel tool and insights into ionic bases of atrioventricular AP differences, and shows how Na + and Ca 2+ homeostases critically mediate abnormal repolarization in AF.
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Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications
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Self-citationIonic mechanisms of electrical remodeling in human atrial fibrillation
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Atrial L-Type Ca 2+ Currents and Human Atrial Fibrillation
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Self-citationMathematical Model of an Adult Human Atrial Cell: The Role of K+Currents in Repolarization
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Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation
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Evidence for Two Components of Delayed Rectifier K+Current in Human Ventricular Myocytes
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Prevention of Atrial Fibrillation: Report From a National Heart, Lung, and Blood Institute Workshop
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A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling
Zhao, Y., Rafatian, N., Feric, N. T., Cox, B. J., Aschar-Sobbi, R., Wang, E. Y., Aggarwal, P., Zhang, B., Conant, G., Ronaldson-Bouchard, K., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.042 · Cited by 610
Voigt, N., Li, N., Wang, Q., Wang, W., Trafford, A. W., Abu-Taha, I., Sun, Q., Wieland, T., Ravens, U., Nattel, S., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.067306 · Cited by 624
Self-citationCarusi, A., Burrage, K., & Rodríguez, B. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01151.2011 · Cited by 102
Recent developments in using mechanistic cardiac modelling for drug safety evaluation
Davies, M. R., Wang, K., Mirams, G. R., Caruso, A., Noble, D., Walz, A., Lavé, T., Schuler, F., Singer, T., & Polonchuk, L. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.02.003 · Cited by 66
Metadata
- Authors
- Grandi, E., Pandit, S. V., Voigt, N., Workman, A. J., Dobrev, D., Jalife, J., & Bers, D. M.
- Venue
- Circulation Research
- Published
- 2011-10-14
- Volume
- 109
- Issue
- 9
- Pages
- 1055-1066
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2531345437
- Cited by
- 365
- References
- 62
- FWCI
- 19.28
- Type
- journal article
- Language
- en
- Open access
- green
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- Grandi, E., Pandit, S. V., Voigt, N., Workman, A. J., Dobrev, D., Jalife, J., & Bers, D. M. (2011). Human Atrial Action Potential and Ca 2+ Model: Sinus Rhythm and Chronic Atrial Fibrillation. Circulation Research. https://doi.org/10.1161/circresaha.111.253955
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