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 a Marie NOVÁKOVÁ

Základní údaje

Originální název

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

Autoři

PÁSEK, Michal a Marie NOVÁKOVÁ

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.900 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

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

Štítky

14110515, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 9. 2025 12:39, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

MUNI/A/1641/2024, interní kód MU

Název: Od buňky k pacientovi II

Investor: Masarykova univerzita, Od buňky k pacientovi II

NU22-02-00348, projekt VaV

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

Investor: Ministerstvo zdravotnictví ČR, Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus, Podprogram 1 - standardní

Citovat

PÁSEK, Michal a Marie NOVÁKOVÁ. Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling. Nature Scientific Reports. Berlin: NATURE RESEARCH, 2025, roč. 15, č. 1, s. 1-13. ISSN 2045-2322. Dostupné z: 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 a Marie NOVÁKOVÁ. Reassessment of mechanical restitution in guinea pig cardiomyocytes through refined computational modelling. \textit{Nature Scientific Reports}. Berlin: NATURE RESEARCH, 2025, roč.~15, č.~1, s.~1-13. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/s41598-025-14815-1.

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