Reassessment of mechanical restitution in guinea pig
cardiomyocytes through refined computational modelling

J 2025

Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling

PÁSEK, Michal and Marie NOVÁKOVÁ

Basic information

Original name

Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling

Authors

PÁSEK, Michal (203 Czech Republic, belonging to the institution) and Marie NOVÁKOVÁ (203 Czech Republic, belonging to the institution)

Edition

Nature Scientific Reports, Berlin, NATURE RESEARCH, 2025, 2045-2322

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Germany

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.900 in 2024

Organization unit

Faculty of Medicine

DOI

https://doi.org/10.1038/s41598-025-14815-1

UT WoS

001547178400020

EID Scopus

2-s2.0-105012937813

Keywords in English

Mechanical restitution; Guinea pig cardiomyocyte; Mathematical model; Calcium current; Ryanodine receptor

Abstract

In the original language

Mechanical restitution (MR) represents the time recovery of the heart muscle's ability to contract. Despite intensive research, some aspects of MR remain unclear. To describe MR in guinea pig cardiac muscle, we modified our published mathematical model of guinea pig ventricular cardiomyocyte and supplemented it with a description of cellular contraction. To achieve the best agreement between the model simulations and available experimental data, some model parameters were optimised. The model enables the simulation of the experimentally observed fast onset of recovery of action potential duration, L-type Ca2+ current amplitude, and isometric force. The performed simulations and analyses of model data showed that the high time constant of voltage-dependent inactivation of L-type Ca2+ channels used in previously published models (similar to 600 ms at resting voltage) is not consistent with the initial steep rise of the MR curve in guinea pig cardiomyocytes. It also suggests that the adaptation rate of ryanodine receptors, which was set differently in the previous models, is fast (similar to 100 s(-1)). Finally, analysis of the effect of a 50% reduction in membrane currents on MR revealed a marked dependence on stimulation frequency. At 1 Hz, only the reduction of I-NaCa and I-NaK significantly affected the MR course.

Links

MUNI/A/1641/2024, interní kód MU

Name: Od buňky k pacientovi II

Investor: Masaryk University, From the cell to the patient

NU22-02-00348, research and development project

Name: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Cite

PÁSEK, Michal and Marie NOVÁKOVÁ. Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling. Nature Scientific Reports. Berlin: NATURE RESEARCH, 2025, vol. 15, No 1, p. 1-13. ISSN 2045-2322. Available from: https://doi.org/10.1038/s41598-025-14815-1.

@article{2514957,
   author = {Pásek, Michal and Nováková, Marie},
   article_location = {Berlin},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41598-025-14815-1},
   keywords = {Mechanical restitution; Guinea pig cardiomyocyte; Mathematical model; Calcium current; Ryanodine receptor},
   language = {eng},
   issn = {2045-2322},
   journal = {Nature Scientific Reports},
   title = {Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling},
   url = {https://www.nature.com/articles/s41598-025-14815-1},
   volume = {15},
   year = {2025}
}

TY  - JOUR
ID  - 2514957
AU  - Pásek, Michal - Nováková, Marie
PY  - 2025
TI  - Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling
JF  - Nature Scientific Reports
VL  - 15
IS  - 1
SP  - 1-13
EP  - 1-13
PB  - NATURE RESEARCH
SN  - 20452322
KW  - Mechanical restitution
KW  - Guinea pig cardiomyocyte
KW  - Mathematical model
KW  - Calcium current
KW  - Ryanodine receptor
UR  - https://www.nature.com/articles/s41598-025-14815-1
N2  - Mechanical restitution (MR) represents the time recovery of the heart muscle's ability to contract. Despite intensive research, some aspects of MR remain unclear. To describe MR in guinea pig cardiac muscle, we modified our published mathematical model of guinea pig ventricular cardiomyocyte and supplemented it with a description of cellular contraction. To achieve the best agreement between the model simulations and available experimental data, some model parameters were optimised. The model enables the simulation of the experimentally observed fast onset of recovery of action potential duration, L-type Ca2+ current amplitude, and isometric force. The performed simulations and analyses of model data showed that the high time constant of voltage-dependent inactivation of L-type Ca2+ channels used in previously published models (similar to 600 ms at resting voltage) is not consistent with the initial steep rise of the MR curve in guinea pig cardiomyocytes. It also suggests that the adaptation rate of ryanodine receptors, which was set differently in the previous models, is fast (similar to 100 s(-1)). Finally, analysis of the effect of a 50% reduction in membrane currents on MR revealed a marked dependence on stimulation frequency. At 1 Hz, only the reduction of I-NaCa and I-NaK significantly affected the MR course.
ER  -

PÁSEK, Michal and Marie NOVÁKOVÁ. Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling. \textit{Nature Scientific Reports}. Berlin: NATURE RESEARCH, 2025, vol.~15, No~1, p.~1-13. ISSN~2045-2322. Available from: https://doi.org/10.1038/s41598-025-14815-1.

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