Abstract
Atrial cardiomyocytes demonstrate a wide spectrum of patient-specific, tissue-specific, and pathology-specific Action potential (AP) phenotypes due to differences in protein expression and posttranslational modifications. Accurate simulation of the AP excitation and propagation in healthy or diseased atria requires a mathematical model capable of reproducing all the differences by parameter rescaling. In the present study, we have benchmarked two widely used electrophysiological models of the human atrium: the Maleckar and the Grandi models. In particular, patch-clamp AP recordings from human atrial myocytes were fitted by the genetic algorithm (GA) to test the models’ versatility. We have shown that the Maleckar model results in a more accurate fitting of heart rate dependence of action potential duration (APD) and resting potential (RP). On the other hand, both models demonstrate the poor fitting of the plateau phase and spike-and-dome morphologies. We propose that modifications to L-type calcium current–voltage relationships are required to improve atrial models’ fidelity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Benjamin, E.J., Wolf, P.A., D’Agostino, R.B., Silbershatz, H., Kannel, W.B., Levy, D.: Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation 98(10), 946–952 (1998)
Steffel, J., Verhamme, P., Potpara, T.S., Albaladejo, P., Antz, M., Desteghe, L., Haeusler, K.G., Oldgren, J., Reinecke, H., Roldan-Schilling, V., Rowell, N.: The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur. Heart J. 39(16), 1330–1393 (2018)
Boyle, P.M., Zghaib, T., Zahid, S., Ali, R.L., Deng, D., Franceschi, W.H., Hakim, J.B., Murphy, M.J., Prakosa, A., Zimmerman, S.L., Ashikaga, H., Marine, J.E., Kolandaivelu, A., Nazarian, S., Spragg, D.D., Calkins, H., Trayanova, N.A.: Computationally guided personalized targeted ablation of persistent atrial fibrillation. Nat. Biomed. Eng. 3(11), 870–879 (2019)
Corrado, C., Williams, S., Karim, R., Plank, G., O’Neill, M., Niederer, S.: A work flow to build and validate patient specific left atrium electrophysiology models from catheter measurements. Med. Image Anal. 47, 153–163 (2018)
Sánchez, C., Bueno-Orovio, A., Wettwer, E., Loose, S., Simon, J., Ravens, U., Pueyo, E., Rodriguez, B.: Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation. PLoS ONE 9(8), e105897 (2014)
Fermini, B.E., Wang, Z.H., Duan, D.A., Nattel, S.T.: Differences in rate dependence of transient outward current in rabbit and human atrium. Am. J. Physiol. Heart Circulatory Physiol. 263(6), H1747–H1754 (1992)
Van Wagoner, D.R., Pond, A.L., Lamorgese, M., Rossie, S.S., McCarthy, P.M., Nerbonne, J.M.: Atrial L-type Ca2+ currents and human atrial fibrillation. Circ. Res. 85(5), 428–436 (1999)
Voigt, N., Li, N., Wang, Q., Wang, W., Trafford, A.W., Abu-Taha, I., Sun, Q., Wieland, T., Ravens, U., Nattel, S., Wehrens, X.H., Dobrev, D.: Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 125(17), 2059–2070 (2012)
Wettwer, E., Hála, O., Christ, T., Heubach, J.F., Dobrev, D., Knaut, M., Varró, A., Ravens, U.: Role of I Kur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation. Circulation 110(16), 2299–2306 (2004)
Schmidt, C., Wiedmann, F., Voigt, N., Zhou, X.B., Heijman, J., Lang, S., Albert, V., Kallenberger, S., Ruhparwar. A., Szabo, G., Kallenbach, K., Karck, M., Borggrefe, M., Biliczki, P., Ehrlich, J.R., Baczko, I., Lugenbiel, P., Schweizer, P.A., Donner, B.C., Katus, H.A., Dobrev, D., Thomas, D.: Upregulation of K2P3. 1K+ current causes action potential shortening in patients with chronic atrial fibrillation. Circulation 132(2), 82–92 (2015)
Schmidt, C., Wiedmann, F., Zhou, X.B., Heijman, J., Voigt, N., Ratte, A., Lang, S., Kallenberger, S.M., Campana, C., Weymann, A., De Simone, R., Szabo, G., Ruhparwar, A., Kallenbach, K., Karck, M., Ehrlich, J.R., Baczko, I., Borggrefe, M., Ravens, U., Dobrev, D., Katus, H.A., Thomas, D.: Inverse remodelling of K2P3.1 K+ channel expression and action potential duration in left ventricular dysfunction and atrial fibrillation: implications for patient-specific antiarrhythmic drug therapy. Eur. Heart J. 38, 1764–1774 (2017)
Voigt, N., Heijman, J., Wang, Q., Chiang, D.Y., Li, N., Karck, M., Wehrens, X.H., Nattel, S., Dobrev, D.: Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation. Circulation 129(2), 145–156 (2014)
Wilhelms, M., Hettmann, H., Maleckar, M.M.C., Koivumäki, J.T., Dössel, O., Seemann, G.: Benchmarking electrophysiological models of human atrial myocytes. Front. Physiol. 3, 487 (2013)
O’Hara, T., Virág, L., Varró, A., Rudy, Y.: Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation. PLoS Comput. Biol. 7(5), e1002061 (2011)
Smirnov, D., Pikunov, A., Syunyaev, R., Deviatiiarov, R., Gusev, O., Aras, K., Gams, A., Koppel, A., Efimov, I.R.: Genetic algorithm-based personalized models of human cardiac action potential. PLoS ONE 15(5), e0231695 (2020)
Maleckar, M.M., Greenstein, J.L., Trayanova, N.A., Giles, W.R.: Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium. Prog. Biophys. Mol. Biol. 98(2–3), 161–170 (2008)
Grandi, E., Pandit, S.V., Voigt, N., Workman, A.J., Dobrev, D., Jalife, J., Bers, D.M.: Human atrial action potential and Ca2+ model: sinus rhythm and chronic atrial fibrillation. Circ. Res. 109(9), 1055–1066 (2011)
Fakuade, F.E., Steckmeister, V., Seibertz, F., Gronwald, J., Kestel, S., Menzel, J., Pronto, J.R.D., Taha, K., Haghighi, F., Kensah, G., Pearman, C.M., Wiedmann, F., Teske, A.J., Schmidt, C., Dibb, K.M., El-Essawi, A., Danner, B.C., Baraki, H., Schwappach, B., Kutschka, I., Mason, F.E., Voigt, N.: Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation. Cardiovasc. Res. cvaa162 (2020)
Nattel, S., Heijman, J., Zhou, L., Dobrev, D.: Molecular basis of atrial fibrillation pathophysiology and therapy: a translational perspective. Circ. Res. 127(1), 51–72 (2020)
Bosch, R.F., Zeng, X., Grammer, J.B., Popovic, K., Mewis, C., Kühlkamp, V.: Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc. Res. 44(1), 121–131 (1999)
Aras, K.K., Faye, N.R., Cathey, B., Efimov, I.R.: Critical volume of human myocardium necessary to maintain ventricular fibrillation. Circ. Arrhythmia Electrophysiol. 11(11), e006692 (2018)
Gaborit, N., Steenman, M., Lamirault, G., Meur, N.L., Bouter, S.L., Lande, G., Léger, J., Charpentier, F., Christ, T., Dobrev, D., Escande, D., Nattel, S., Demolombe, S.: Human atrial ion channel and transporter subunit gene-expression remodeling associated with valvular heart disease and atrial fibrillation. Circulation 112, 471–481 (2005)
Gaborit, N., Le Bouter, S., Szuts, V., Varro, A., Escande, D., Nattel, S., Demolombe, S.: Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. J. Physiol. 582(2), 675–693 (2007)
Li, G.R., Nattel, S.: Properties of human atrial ICa at physiological temperatures and relevance to action potential. Am. J. Physiol. Heart Circulatory Physiol. 272(1), H227–H235 (1997)
Magyar, J., Iost, N., Körtvély, Á., Bányász, T., Virág, L., Szigligeti, P., Varró, A., Opincariu, M., Szécsi, J., Papp, J.G., Nánási, P.P.: Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes. Pflügers Arch. 441(1), 144–149 (2000)
Tomek, J., Bueno-Orovio, A., Passini, E., Zhou, X., Minchole, A., Britton, O., Bartolucci, C., Severi, S., Shrier, A., Virag, L., Varro, A., Rodriguez, B.: Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block. Elife 8, e48890 (2019)
Kettlewell, S., Saxena, P., Dempster, J., Colman, M.A., Myles, R.C., Smith, G.L., Workman, A.J.: Dynamic clamping human and rabbit atrial calcium current: narrowing ICaL window abolishes early afterdepolarizations. J. Physiol. 597(14), 3619–3638 (2019)
Acknowledgements
The authors thank Ines Müller and Stefanie Kestel for excellent technical assistance and the cardiac surgeons of the Department of Thoracic and Cardiovascular Surgery, University Medical Center Göttingen for kindly providing human atrial tissue samples.
This work was supported by grants from the German Center for Cardiovascular Research (DZHK), the Deutsche Forschungsgemeinschaft to Niels Voigt (DFG, German Research Foundation, VO 1568/3-1, IRTG1816 RP12, SFB1002 TPA13 and under Germany’s Excellence Strateg—EXC 2067/1-390729940), from the from the Else-Kröner-Fresenius Foundation to Niels Voigt (EKFS 2016_A20), from NIH/NHLBI (U01 HL141074) and Leducq Foundation (RHYTHM) to Igor R. Efimov, computer model optimization was supported by Russian Scientific Foundation grant 18-71-10058 to Roman A. Syunyaev.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this paper
Cite this paper
Pikunov, A.V., Syunyaev, R.A., Steckmeister, V., Kutschka, I., Voigt, N., Efimov, I.R. (2021). Personalization of Mathematical Models of Human Atrial Action Potential. In: Favorskaya, M.N., Favorskaya, A.V., Petrov, I.B., Jain, L.C. (eds) Smart Modelling For Engineering Systems. Smart Innovation, Systems and Technologies, vol 214. Springer, Singapore. https://doi.org/10.1007/978-981-33-4709-0_19
Download citation
DOI: https://doi.org/10.1007/978-981-33-4709-0_19
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-33-4708-3
Online ISBN: 978-981-33-4709-0
eBook Packages: Intelligent Technologies and RoboticsIntelligent Technologies and Robotics (R0)