Skip to content
Microsystems, Electronics and Acoustics
ISSN 2523-4447 · e‑ISSN 2523-4455 Open Access · CC BY-SA 4.0
Vol. 31 · Issue 1 · 2026 May 4, 2026 Electronic Systems and Signals

Modeling the Impact of Temperature on the Electrical Activity of Cardiac Cells: Identification of Key Ionic Currents

VI
Vitalii O. Ivashchuk Corresponding National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” Ukraine
NI
PhD, Assoc. Prof. Nataliia Heorhiivna Ivanushkina National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute” Ukraine
Pages357181.1-357181.13 PublishedMay 4, 2026 LicenseOpen Access
VOL 31 · ISS 1 · 2026 View issue

Abstract

This study presents the development of a modified electrophysiological model of a human epicardial cardiomyocyte, achieved by taking into account the temperature effects on the kinetics and conductance of ion channels using parameter-specific Q10 coefficients. Based on the modified model, a temperature sensitivity analysis was performed to identify the key ionic mechanisms that regulate thermal adaptation of action potential duration (APD). The simulation was performed in the temperature range of 25–45 °C using a hybrid approach that combines local and global sensitivity analyses. Local analysis was performed by calculating elasticity coefficients to evaluate the impact of individual temperature parameters on APD. Global analysis was carried out using the Morris method of elementary effects to rank parameters by their influence and to identify non-linear interactions. The results demonstrate that the rapid delayed rectifier potassium current (IKr) plays a predominant role in the modulation of APD. It accounts for approximately 85% of the total APD shortening when the temperature rises to 42 °C, where APD decreases by 22.03% (from 270.91 ms to 211.24 ms). Under deep hypothermia (25 °C), a 52.47% prolongation of the action potential (AP) and a 169% increase in the repolarization phase duration were observed. Furthermore, the study reveals that at moderate hypothermia (30 °C), non-linear interactions between various ion channels become a decisive factor. A significant contribution of the sodium-calcium exchanger (NCX) and the late sodium current (INaL) was demonstrated at lower temperatures, confirming the temperature dependence of these interactions. These findings underscore the critical role of the human Ether-à-go-go-Related Gene (hERG) in the thermal adaptation of the ventricular myocardium and provide a computational framework for investigating the mechanisms of thermo-induced arrhythmias.

Keywords

References

  1. Stefanu Buzatu, “The temperature-induced changes in membrane potential - PubMed,” Riv Biol, vol. 102(2), pp. 199–217, 2009, PMID: 20077389.
  2. J. Chi et al., “Hygrothermal stress increases malignant arrhythmias susceptibility by inhibiting the LKB1-AMPK-Cx43 pathway,” Scientific Reports 2024 14:1, vol. 14, no. 1, pp. 5010-, Feb. 2024, PMID: 38424223.
  3. M. Zaltieri, C. Massaroni, F. M. Cauti, and E. Schena, “Techniques for Temperature Monitoring of Myocardial Tissue Undergoing Radiofrequency Ablation Treatments: An Overview,” Sensors 2021, Vol. 21, Page 1453, vol. 21, no. 4, p. 1453, Feb. 2021, PMID: 33669692.
  4. J. Liu et al., “Heat exposure and cardiovascular health outcomes: a systematic review and meta-analysis,” Lancet Planet. Health, vol. 6, no. 6, pp. e484–e495, Jun. 2022, PMID: 35709806.
  5. J. Tomek et al., “Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block,” Elife, vol. 8, Dec. 2019, PMID: 31868580.
  6. F. Yang and J. Zheng, “High temperature sensitivity is intrinsic to voltage-gated potassium channels,” Elife, vol. 3, p. e03255, 2014, PMID: 25030910.
  7. T. J. A. Allen, “Temperature dependence of macroscopic L-type calcium channel currents in single guinea pig ventricular myocytes,” J. Cardiovasc. Electrophysiol., vol. 7, no. 4, pp. 307–321, 1996, PMID: 8777479.
  8. M. R. Tanner and C. Beeton, “Differences in ion channel phenotype and function between humans and animal models,” Front. Biosci. (Landmark Ed)., vol. 23, no. 1, pp. 43–64, 2018, PMID: 28930537.
  9. Bertil. Hille, Ion channels of excitable membranes. Sinauer Associates, Inc. ; Oxford University Press, 2001. ISBN: 9780197583074
  10. T. Milburn, D. A. Saint, and S. H. Chung, “The temperature dependence of conductance of the sodium channel: implications for mechanisms of ion permeation.,” Recept. Channels, vol. 3, no. 3, pp. 201–211, 1995, PMID: 8821793.
  11. T. Nagatomo et al., “Temperature dependence of early and late currents in human cardiac wild-type and long Q-T ΔKPQ Na+ channels,” https://doi.org/10.1152/ajpheart.1998.275.6.H2016 , vol. 275, no. 6 44-6, 1998, PMID: 9843800.
  12. M. Vornanen, H. A. Shiels, and A. P. Farrell, “Plasticity of excitation–contraction coupling in fish cardiac myocytes,” Comp. Biochem. Physiol. A Mol. Integr. Physiol., vol. 132, no. 4, pp. 827–846, Aug. 2002, PMID: 12095866.
  13. V. A. Maltsev and A. I. Undrovinas, “A Multi-Modal Composition of the Late Na+ Current in Human Ventricular Cardiomyocytes,” Cardiovasc. Res., vol. 69, no. 1, p. 116, Jan. 2005, PMID: 16223473.
  14. M. Mauerhöfer and C. K. Bauer, “Effects of Temperature on Heteromeric Kv11.1a/1b and Kv11.3 Channels,” Biophys. J., vol. 111, no. 3, pp. 504–523, Aug. 2016, PMID: 27508435.
  15. M. Q. Dong, C. P. Lau, Z. Gao, G. N. Tseng, and G. R. Li, “Characterization of recombinant human cardiac KCNQ1/KCNE1 channels (I (Ks)) stably expressed in HEK 293 cells,” J. Membr. Biol., vol. 210, no. 3, pp. 183–192, Mar. 2006, PMID: 16909339.
  16. T. Kiyosue, M. Arita, H. Muramatsu, A. J. Spindler, and D. Noble, “Ionic mechanisms of action potential prolongation at low temperature in guinea-pig ventricular myocytes,” J. Physiol., vol. 468, no. 1, pp. 85–106, Aug. 1993, PMID: 8254536.
  17. S. Radicke et al., “Accessory subunits alter the temperature sensitivity of Kv4.3 channel complexes,” J. Mol. Cell. Cardiol., vol. 56, pp. 8–18, Mar. 2013, DOI: 10.1016/j.yjmcc.2012.12.017.
  18. K. H. W. J. Ten Tusscher, D. Noble, P. J. Noble, and A. V. Panfilov, “A model for human ventricular tissue,” https://doi.org/10.1152/ajpheart.00794.2003 , vol. 286, no. 4 55-4, pp. 1573–1589, 2004, PMID: 14656705.
  19. J. Millet et al., “Thermal modulation of epicardial Ca2+ dynamics uncovers molecular mechanisms of Ca2+ alternans,” Journal of General Physiology, vol. 153, no. 2, Feb. 2021, PMID: 33410862.
  20. Y. Nakamura, Y. Ohya, I. Abe, and M. Fujishima, “Sodium-potassium pump current in smooth muscle cells from mesenteric resistance arteries of the guinea-pig,” J. Physiol., vol. 519, no. Pt 1, p. 203, Aug. 1999, PMID: 10432351.
  21. C. L. Elias, X. H. Xue, C. R. Marshall, A. Omelchenko, L. V. Hryshko, and G. F. Tibbits, “Temperature dependence of cloned mammalian and salmonid cardiac Na+/Ca2+ exchanger isoforms,” https://doi.org/10.1152/ajpcell.2001.281.3.C993 , vol. 281, no. 3 50-3, 2001, PMID: 11502576.
  22. Z. Zhou et al., “Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature,” Biophys. J., vol. 74, no. 1, p. 230, 1998, PMID: 9449325.
  23. J. I. Vandenberg, M. D. Perry, M. J. Perrin, S. A. Mann, Y. Ke, and A. P. Hill, “hERG K(+) channels: structure, function, and clinical significance,” Physiol. Rev., vol. 92, no. 3, pp. 1393–1478, 2012, PMID: 22988594.
  24. B. Pahlavan, N. Buitrago, and F. Santamaria, “Macromolecular rate theory explains the temperature dependence of membrane conductance kinetics,” Biophys. J., vol. 122, no. 3, pp. 522–532, Feb. 2023, PMID: 36567527.
  25. R. M. Daniel and M. J. Danson, “Temperature and the catalytic activity of enzymes: a fresh understanding,” FEBS Lett., vol. 587, no. 17, pp. 2738–2743, Sep. 2013, PMID: 23810865.
  26. M. Clerx, P. Collins, E. de Lange, and P. G. A. Volders, “Myokit: A simple interface to cardiac cellular electrophysiology,” Prog. Biophys. Mol. Biol., vol. 120, no. 1–3, pp. 100–114, Jan. 2016, PMID: 26721671.
  27. A. C. Hindmarsh et al., “SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers,” ACM Transactions on Mathematical Software, vol. 31, no. 3, pp. 363–396, 2005, DOI: 10.1145/1089014.1089020.
  28. A. X. Sarkar and E. A. Sobie, “Regression Analysis for Constraining Free Parameters in Electrophysiological Models of Cardiac Cells,” PLoS Comput. Biol., vol. 6, no. 9, p. e1000914, 2010, PMID: 20824123.
  29. T. O’Hara, L. Virág, A. Varró, and Y. Rudy, “Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation,” PLoS Comput. Biol., vol. 7, no. 5, p. e1002061, 2011, PMID: 21637795.
  30. E. A. Sobie, “Parameter sensitivity analysis in electrophysiological models using multivariable regression,” Biophys. J., vol. 96, no. 4, pp. 1264–1274, Feb. 2009, PMID: 19217846.
  31. M. Balesdent, L. Brevaul, S. Lacaze, S. Missoum, and J. Morio, “Methods for high-dimensional and computationally intensive models,” Estimation of Rare Event Probabilities in Complex Aerospace and Other Systems: A Practical Approach, pp. 109–136, 2016, DOI: 10.1016/B978-0-08-100091-5.00008-3.
  32. E. S. Dietrichs et al., “Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology,” Cardiovasc. Res., vol. 116, no. 13, p. 2081, Nov. 2020, PMID: 32031595.
  33. M. Aguilar and S. Nattel, “The pioneering work of George Mines on cardiac arrhythmias: groundbreaking ideas that remain influential in contemporary cardiac electrophysiology,” J. Physiol., vol. 594, no. 9, p. 2377, May 2016, PMID: 26607760.
  34. A. Crispino et al., “A cross species thermoelectric and spatiotemporal analysis of alternans in live explanted hearts using dual voltage-calcium fluorescence optical mapping,” Physiol. Meas., vol. 45, no. 6, p. 065001, Jun. 2024, PMID: 38772394.
  35. H. Olai et al., “Meta-analysis of targeted temperature management in animal models of cardiac arrest,” Intensive Care Medicine Experimental 2020 8:1, vol. 8, no. 1, pp. 3-, Jan. 2020, PMID: 31953652.
  36. G. Tse, S. T. Wong, V. Tse, and J. M. Yeo, “Restitution analysis of alternans using dynamic pacing and its comparison with S1S2 restitution in heptanol-treated, hypokalaemic Langendorff-perfused mouse hearts,” Biomed. Rep., vol. 4, no. 6, p. 673, Jun. 2016, PMID: 27284405.
  37. “Dynamic and S1S2 restitution curves in the three model versions. Each... | Download Scientific Diagram.” [Online]. Available: https://www.researchgate.net/figure/Dynamic-and-S1S2-restitution-curves-in-the-three-model-versions-Each-panel-represents_fig6_221683402 . [Accessed: 10-Mar-2026].
  38. A. Loppini, A. Barone, A. Gizzi, C. Cherubini, F. H. Fenton, and S. Filippi, “Thermal effects on cardiac alternans onset and development: A spatiotemporal correlation analysis,” Phys. Rev. E, vol. 103, no. 4, p. L040201, Apr. 2021, PMID: 34005953.
  39. R. Majumder, A. Nabizath, M. Nazer, A. V Panfilov, E. Bodenschatz, and Y. Wang, “Electrophysiological characterization of human atria: the understated role of temperature,” bioRxiv, p. 2020.12.07.414573, Dec. 2020, DOI: 10.1101/2020.12.07.414573.
  40. B. Hegyi et al., “Altered Repolarization Reserve in Failing Rabbit Ventricular Myocytes: Calcium and β-Adrenergic Effects on Delayed- and Inward-Rectifier Potassium Currents,” Circ. Arrhythm. Electrophysiol., vol. 11, no. 2, Feb. 2018, PMID: 29437761.
  41. Y. Zhao and J. A. Boulant, “Temperature effects on neuronal membrane potentials and inward currents in rat hypothalamic tissue slices,” J. Physiol., vol. 564, no. Pt 1, pp. 245–257, Apr. 2005, PMID: 15695248.
  42. V. O. Ivashchuk, “Modelyuvannya vplyvu temperatury na elektrychnu aktyvnistʹ sertsevykh klityn [Modeling the influence of temperature on the electrical activity of heart cells].” Igor Sikorsky KPI, 2024, URL: https://ela.kpi.ua/handle/123456789/67891 .
  43. Y. Belhamadia and J. Grenier, “Modeling and simulation of hypothermia effects on cardiac electrical dynamics,” PLoS One, vol. 14, no. 5, p. e0216058, May 2019, PMID: 31050665.
  44. P. P. Kanade, N. E. Oyunbaatar, and D. W. Lee, “Effects of low temperature on electrophysiology and mechanophysiology of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs),” Micro and Nano Systems Letters 2021 9:1, vol. 9, no. 1, pp. 9-, Oct. 2021, DOI: 10.1186/s40486-021-00135-2.
  45. S. Meier, A. Grundland, D. Dobrev, P. G. A. Volders, and J. Heijman, “In-silico analysis of the dynamic regulation of cardiac electrophysiology by Kv11.1 ion-channel trafficking,” J. Physiol., vol. 601, no. 13, p. 2711, Jul. 2023, PMID: 36752166.
  46. M. Varshneya, R. A. Devenyi, and E. A. Sobie, “Slow Delayed Rectifier Current Protects Ventricular Myocytes From Arrhythmic Dynamics Across Multiple Species,” Circ. Arrhythm. Electrophysiol., vol. 11, no. 10, p. e006558, Oct. 2018, PMID: 30354408.
  47. B. Hegyi et al., “Balance Between Rapid Delayed Rectifier K+ Current and Late Na+ Current on Ventricular Repolarization: An Effective Antiarrhythmic Target?,” Circ. Arrhythm. Electrophysiol., vol. 13, no. 4, p. E008130, Apr. 2020, PMID: 32202931.
  48. A. Varró et al., “Cardiac transmembrane ion channels and action potentials: cellular physiology and arrhythmogenic behavior,” Physiol. Rev., vol. 101, no. 3, pp. 1083–1176, Jul. 2021, PMID: 33118864.

License

CCBY-SA 4.0
Creative Commons Attribution 4.0 International

This work is openly licensed — share and adapt freely with attribution to the authors and the journal. View license terms ↗

§ 06 — Related

Similar articles in this journal

Related peer-reviewed studies published in this journal.
View all issues

Quasistatic Identification of The Shading Structure of Solar Panels by The Method of Cardinal Number Vectors

PhD, Assoc. Prof. Olena Olehivna Abakumova, Dr.Sc.(Eng.), Prof. Valerii Yakovych Zhuikov, Mykola O. Lukianov

In the article the problem of identification the shading structure of solar panels is considered. The relevance of the study is conditioned by the necessity of rapid and…

#solar panels #photovoltaic surface #shadow structure modeling #quasistatic identification
p. 362283.1-362283.7
10.20535/2523-4455.mea.362283

A A Complex Method for Non-invasive Fetal Electrocardiogram Signal Extraction and Cardiac Arrhythmia Classification

Dmytro A. Shevchuk, PhD, Assoc. Prof. Nataliia Heorhiivna Ivanushkina

This study is devoted to the development of a complex method for extracting the fetal electrocardiogram (fECG) from non-invasive abdominal recordings and for the…

#abdominal electrocardiogram #fetal electrocardiogram #arrhythmia #blind source separation
p. 356487.1-356487.11
10.20535/2523-4455.mea.356487

Simulation Modeling of a Filter-Compensating Converter for a Three-Phase Three-Wire Network

Ivan Andriiovych Vakulenko, PhD, Assoc. Prof. Dmytro Anatoliiovych Mykolaiets, PhD, Assoc. Prof. Kateryna Serhiivna Klen

This paper addresses the critical issue of power quality degradation in modern power systems caused by the proliferation of non-linear loads. The study focuses on the…

#filter-compensating converter #three-phase three-wire network #power quality #total harmonic distortion
p. 361138.1-361138.6
10.20535/2523-4455.mea.361138

Most read articles by the same author(s)

Similar Articles

1-10 of 87

You may also start an advanced similarity search for this article.