Solving the Inverse Problem of Relationship Between Action Potentials and Field Potentials in Cardiac Cells




MEA system, cardiomyocyte, action potential, field potential, inverse problem of electrocardiography, cardiac toxicity assessment, lab-on-chip technology, human-induced pluripotent stem cells, wavelet denoising


Multiple electrode array (MEA) systems are the instrument platforms being used for cardiac extracellular electrophysiology investigation. Key applications of MEA technology are disease modeling and screening of drug effects. To solve these problems the efforts of many scientists are directed to signal processing and analysis of field potentials (FP) measured with MEA systems. However, it should be noted the complexity of interpretation of MEA information in non-invasive field potentials measurements of cardiac cells compared to invasive action potential (AP) recordings obtained using patch clamp technology. This study is devoted to the mathematical determination of the relationship between the signals of the electrical activity of cardiomyocytes: internal AP and external FP. Derivation of equations for transfer functions between AP and FP is based on field theory. This article provides a solution to the inverse problems of the relationship between AP and FP. Numerical experiments demonstrate the results of the inverse transformation of simulated field potentials signals. To denoise the potentials of the extracellular field of cardiomyocytes, the method combining wavelet transform and processing in eigensubspaces of cardiac cycles is used. The proposed method, based on transfer functions, can be used to determine AP parameters and expand the capabilities of data analysis in MEA systems for diagnosing heart disease and assessing cardiac toxicity during drug development.

Author Biographies

N. G. Ivanushkina , National Technical University of Ukraine "Igor Sikorsky Kyiv Polytechnic Institute", Kyiv

к.т.н., доцент

K. O. Ivanko , National Technical University of Ukraine "Igor Sikorsky Kyiv Polytechnic Institute", Kyiv

к.т.н., доцент

Y. V. Prokopenko , National Technical University of Ukraine "Igor Sikorsky Kyiv Polytechnic Institute", Kyiv

д.т.н., доцент



Garma L. D., Matino L., Melle G., Moia F., De Angelis F., Santoro F., Dipalo M. (2019). Cost-effective and multifunctional acquisition system for in vitro electrophysiological investigations with multielectrode arrays. PLoS ONE, 14(3): e0214017. DOI:10.1371/journal.pone.0214017.

Asakura K., Hayashi S., Ojima A. et al. (2015). Improvement of acquisition and analysis methods in multi-electrode array experiments with iPS cell-derived cardiomyocytes. Journal of Pharmacological and Toxicological Methods, Volume 75, pp. 17-26. DOI: 10.1016/j.vascn.2015.04.002.

Jäckel D., Bakkum D. J., Russell T. L. et al. (2017). Combination of High-density Microelectrode Array and Patch Clamp Recordings to Enable Studies of Multisynaptic Integration. Scientific Reports, Vol. 7, Article number: 978. DOI:10.1038/s41598-017-00981-4.

Reinhard K., Tikidji-Hamburyan A., Seitter H., Idrees S., Mutter M., Benkner B., Münch T. A. (2014). Step-By-Step Instructions for Retina Recordings with Perforated Multi Electrode Arrays. PLoS ONE. DOI: 10.1371/journal.pone.0106148.

Fermini B., Fossa A. A. (2003). The impact of drug-induced QT interval prolongation on drug discovery and development. Nature Reviews. Drug Discovery, 2(6), pp. 439-447. doi: 10.1038/nrd1108.

Roden D. M. (2000). Acquired Long QT Syndromes and the Risk of Proarrhythmia. Journal of Cardiovascular Electrophysiology, Vol. 11, Iss. 8, pp. 938-940. doi:10.1111/j.1540-8167.2000.tb00077.x

Braam S. R., Tertoolen L., Van de Stolpe A., Meyer T., Passier R., Mummery C. L. (2010). Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res., Vol. 4, Iss. 2, pp. 107-116. DOI:10.1016/j.scr.2009.11.004.

Nachimuthu S., Assar M. D., Schussler J. M. (2012). Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf., Vol. 3, Iss. 5, pp. 241-253. DOI: 10.1177/2042098612454283.

Tsuji Y., Opthof T., Yasui K. et al. (2002). Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block. Circulation, Vol. 106(15), pp. 2012-2018. DOI: 10.1161/01.cir.0000031160.86313.24.

Li M., Ramos L.G. (2017). Drug-Induced QT Prolongation and Torsades de Pointes. Pharmasy & Therapeutics, Vol. 42(7), pp. 473-477, PMID: 28674475.

Champeroux P., Martel E., Vannier C., Blanc V., Leguennec J. Y., Fowler J., Richard S. (2000). The preclinical assessment of the risk for QT interval prolongation. Therapie, Vol. 55(1), pp. 101-109, PMID: 10860008.

Wallis R. M. (2010). Integrated risk assessment and predictive value to humans of non-clinical repolarization assays. British Jornal of Pharmacology, Vol. 159, Iss. 1, pp. 115–121. doi: 10.1111/j.1476-5381.2009.00395.x.

Tertoolen L. G. J., Braam S. R., van Meer B. J., Passier R., Mummerya C. L. (2018). Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun., Vol. 497, Iss. 4, pp. 1135–1141. doi: 10.1016/j.bbrc.2017.01.151.

Navarrete E. G., Liang P., Lan F. et al. (2013). Screening drug-induced arrhythmia using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation., Vol. 128, Iss. 11 Suppl 1, pp. S3-13. DOI: 10.1161/circulationaha.112.000570.

Yamazaki D. et al. (2018). Proarrhythmia risk prediction using human induced pluripotent stem cell-derived cardiomyocytes. Journal of Pharmacological Sciences, Vol. 136, Iss. 4, pp. 249-256. DOI:10.1016/j.jphs.2018.02.005.

Mandenius C. F., Steel D., Noor F. et al. (2011). Cardiotoxicity testing using pluripotent stem cell-derived human cardiomyocytes and state-of-the-art bioanalytics: A review. Journal of Applied Toxicology, Vol. 31, Iss. 3, pp. 191–205. DOI:10.1002/jat.1663.

Takasuna K., Asakura K., Araki S. et al. (2016). Comprehensive in vitro cardiac safety assessment using human stem cell technology: Overview of CSAHi HEART initiative. Journal of Pharmacological and Toxicological Methods, Vol. 83, pp. 42-54. DOI: 10.1016/j.vascn.2016.09.004.

Ando H., Yoshinaga T., Yamamoto W. et al. (2017). A new paradigm for drug-induced torsadogenic risk assessment using human iPS cell-derived cardiomyocytes. J Pharmacol Toxicol Methods., Vol. 84, pp. 111-127. DOI: 10.1016/j.vascn.2016.12.003.

Plonsey R., Barr R. C. (2007). Bioelectricity. A Quantitative Approach, third ed. Springer, Boston, MA, p. 528. DOI: 10.1007/978-0-387-48865-3.

Ivanko K., Ivanushkina N. and Prokopenko Y. (2017). Simulation of action potential in cardiomyocytes. 2017 IEEE 37th International Conference on Electronics and Nanotechnology (ELNANO), pp. 358-362, doi: 10.1109/ELNANO.2017.7939777.

Ivanushkina N., Ivanko K., Prokopenko Y., Redaelli A., Timofeyev V., Ivanushkina M. (2019). Approach for Cardiac Action Potential Detection from Noised Recordings. 2019 IEEE 39th International Scientific Conference on Electronics and Nanotechnology (ELNANO), pp. 530-535. doi:10.1109/ELNANO.2019.8783603.

Janmey P. A., Winer J. P., Weise l. W. (2009). Fibrin gels and their clinical and bioengineering applications. Journal of the Royal Society Interface, Vol. 6, Iss. 30, pp. 1–10. doi:10.1098/rsif.2008.0327.

Pahlavan S. (2019). hPSC-CM. IEEE Dataport. DOI:10.21227/czwn-8g10.




How to Cite

Ivanushkina , N. G., Ivanko , K. O., Shpotak , M. O. and Prokopenko , Y. V. (2021) “Solving the Inverse Problem of Relationship Between Action Potentials and Field Potentials in Cardiac Cells”, Visnyk NTUU KPI Seriia - Radiotekhnika Radioaparatobuduvannia, (85), pp. 53-59. doi: 10.20535/RADAP.2021.85.53-59.



Radioelectronics Medical Technologies

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