Estimation of Multiple Cardiac Cells’ Action Potentials From Extracellular Field Potentials
DOI:
https://doi.org/10.20535/RADAP.2023.93.70-77Keywords:
action potentials, field potentials, signal reconstruction, signal synchronicity, numerical modelling, cellular electrophysiology, microelectrode arrayAbstract
Modern biomedical technologies use a combination of microelectrode array (MEA) systems and artificially grown cells to study disease mechanisms and test drug effects. MEA systems measure extracellular field potentials (FPs) of cell cultures or tissues, but they cannot record intracellular action potentials (APs) without some modifications or additional devices, limiting the depth of electrophysiological analysis. One of the possible solutions to the inability of MEA systems to measure APs is to mathematically reconstruct them using recorded FPs. However, accurately reconstructing APs of multiple cells is challenging task, which is complicated by many factors such as the number of cells, synchronicity of their APs, identification of their electrophysiological parameters, and noise. This paper aims to address the mathematical problem of AP synchronicity, asynchronicity and partial synchronicity between multiple cells. In this study, mathematical techniques were employed to derive a system of equations capable of reconstructing the APs of N cells simultaneously, using the FPs recorded with N+1 electrodes. The equations take into account the number of cells, synchronicity and variation of their APs and specific electrical properties of the cells and the medium. In numerical experiments the equations were applied to reconstruct APs from FPs for cases with different types of synchronicity in noise-free and noisy conditions. The reconstructed APs, when combined with recorded FPs, expand the number of electrophysiological characteristics available for cardiotoxicity assessment in MEA systems.
References
References
Novellino, A., Scelfo, B., Palosaari, T., et al. (2011). Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals. Frontiers in Neuroengineering, Vol. 4. DOI: 10.3389/fneng.2011.00004.
Mulder, P., de Korte, T., Dragicevic, E., et al. (2018). Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report. Journal of Pharmacological and Toxicological Methods, Vol. 91, pp.36-42. DOI: 10.1016/j.vascn.2018.01.003.
Shih, H. T. (1994). Anatomy of the action potential in the heart. Texas Heart Institute Journal, Vol. 21, Iss. 1, pp. 30-41.
Boyett, M. R., Honjo, H. and Kodama, I. (2000). The sinoatrial node, a heterogeneous pacemaker structure. Cardiovascular research, Vol. 47, Iss. 4, pp. 658-687. DOI: 10.1016/s0008-6363(00)00135-8.
Tertoolen, L. G. J., Braam, S. R., Van Meer, B. J., Passier, R. and Mummery, 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. Biochemical and Biophysical Research Communications, Vol. 497, Iss. 4, pp. 1135-1141. DOI: 10.1016/j.bbrc.2017.01.151.
Duan, X., Gao, R., Xie, P., et al. (2012). Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nature Nanotechnology, Vol. 7, Iss. 3, pp.174-179. DOI: 10.1038/nnano.2011.223.
Cerea, A., Caprettini, V., Bruno, G., et al. (2018). Selective intracellular delivery and intracellular recordings combined in MEA biosensors. Lab on a Chip, Iss. 22, pp. 3492-3500. DOI: 10.1039/C8LC00435H.
Nick, C., Joshi, R., Schneider, J. J. and Thielemann, C. (2012). Three-Dimensional Carbon Nanotube Electrodes for Extracellular Recording of Cardiac Myocytes. Biointerphases, Vol. 7, Iss. 1. DOI: 10.1007/s13758-012-0058-2.
Dipalo, M., Amin, H., Lovato, L., et al. (2017). Intracellular and Extracellular Recording of Spontaneous Action Potentials in Mammalian Neurons and Cardiac Cells with 3D Plasmonic Nanoelectrodes. Nano letters, Vol. 17, Iss. 6, pp. 3932-3939. DOI: 10.1021/acs.nanolett.7b01523.
Iachetta, G., Melle, G., Colistra, N., Tantussi, F., De Angelis, F. and Dipalo, M. (2022). Chronic cardiotoxicity assessment by cell optoporation on microelectrode arrays. bioRxiv, pp. 2022-06. DOI: 10.1101/2022.06.20.496820.
Jans, D., Callewaert, G., Krylychkina, O., et al. (2017). Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes. Journal of Pharmacological and Toxicological Methods, Vol. 87, pp. 48-52. DOI: 10.1016/j.vascn.2017.05.003.
Zlochiver, V., Kroboth, S. L., Beal, C. R., Cook, J. A. and Joshi-Mukherjee, R. (2019). Human iPSC-Derived Cardiomyocyte Networks on Multiwell Micro-electrode Arrays for Recurrent Action Potential Recordings. JoVE (Journal of Visualized Experiments), (149), p. e59906. DOI: 10.3791/59906.
Zhang, Z., Zheng, T. and Zhu, R. (2020). Single-cell individualized electroporation with real-time impedance monitoring using a microelectrode array chip. Microsystems & Nanoengineering, Vol. 6, Article number: 81. DOI: 10.1038/s41378-020-00196-0.
Davis, A. A., Farrar, M. J., Nishimura, N., Jin, M. M. and Schaffer, C. B. (2013). Optoporation and Genetic Manipulation of Cells Using Femtosecond Laser Pulses. Biophysical Journal, Vol. 105, Iss. 4, pp. 862-871. DOI: 10.1016/j.bpj.2013.07.012.
Ivanushkina, N. G., Ivanko, K. O., Shpotak, M. O. and Prokopenko, Y. V. (2022). Reconstruction of Action Potentials of Cardiac Cells from Extracellular Field Potentials. Radioelectronics and Communications Systems, Vol. 65, Iss. 7, pp. 354-364. DOI: 10.3103/S0735272722090047.
Visone, R., Ugolini, G. S., Cruz-Moreira, D., et al. (2021). Micro-electrode channel guide (µECG) technology: an online method for continuous electrical recording in a human beating heart-on-chip. Biofabrication, Vol. 13, Iss. 3, 035026. DOI: 10.1088/1758-5090/abe4c4.
Shpotak, M., Ivanushkina, N., Ivanko, K. and Prokopenko, Y. (2022). A Model for Simulation of Human Sinoatrial Node Action Potential. 2022 IEEE 41st International Conference on Electronics and Nanotechnology (ELNANO), pp. 422-425. DOI: 10.1109/elnano54667.2022.9927001.
Pohl, A., Wachter, A., Hatam, N. and Leonhardt, S. (2016). A computational model of a human single sinoatrial node cell. Biomedical Physics & Engineering Express, Vol. 2, Iss. 3, 035006. DOI: 10.1088/2057-1976/2/3/035006.
Visone, R., Talò, G., Occhetta, P., et al. (2018). A microscale biomimetic platform for generation and electro-mechanical stimulation of 3D cardiac microtissues. APL Bioengineering, Vol. 2, Iss. 4. DOI: 10.1063/1.5037968.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Михайло Шпотак
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
