Functional consequences of different distribution of NCX and
PMCA between t-tubular and surface membranes in a model of the
human ventricular cardiomyocyte

a 2023

Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte

PÁSEK, Michal, Markéta BÉBAROVÁ a Jiří ŠIMURDA

Základní údaje

Originální název

Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte

Autoři

PÁSEK, Michal (203 Česká republika, garant, domácí), Markéta BÉBAROVÁ (203 Česká republika, domácí) a Jiří ŠIMURDA (203 Česká republika)

Vydání

47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Dánsko

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14110/23:00134666

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

human ventricular cardiomyocyte; NCX; PMCA

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 4. 2024 12:29, Mgr. Tereza Miškechová

Anotace

V originále

Background: The sarcolemmal Ca2+ efflux pathways, Na+-Ca2+ exchanger (NCX), and Ca2+-ATPase (PMCA), play a crucial role in the regulation of intracellular Ca2+ load and Ca2+ transient. Experimental studies published so far have indicated that the t-tubular fractions of NCX and PMCA (fNaCa,t and fpCa,t) in ventricular myocytes might be lower than 0.3 as well as higher than 0.9. Moreover, the membrane distribution of both transporters appears to vary during development and cardiac diseases. However, the consequences of changes in NCX and PMCA distribution between the t-tubular and surface membranes of human ventricular cardiomyocytes have not yet been elucidated. Methods: We addressed this point by using a mathematical model of the human ventricular myocyte incorporating t-tubules, dyadic spaces, and subsarcolemmal spaces. Effects of various combinations of fNaCa,t and fpCa,t were explored using values between 0.2 and 1 as reported in animal experiments under normal and pathological conditions. For numerical solution, the computational software MATLAB version 7.2 (MathWorks, Natick, MA, USA) was used. Results: Small variations in the duration of action potentials (≤ 2%), but a substantial increase in the peak value of cytosolic Ca2+ transient (up to 18%) were observed in the model when NCX and PMCA were redistributed to the t-tubular or surface membranes. This effect was caused by an increase of Ca2+ load in the sarcoplasmic reticulum due to an increase of Ca2+ concentration in the cytosol (after the termination of Ca2+ transient) in response to the reduced activity of NCX and PMCA under the membrane domain where these transporters predominated. Conclusion: These results indicate that redistribution of both transporters between the t-tubular and surface membranes may contribute to the changes in the inotropic state of human ventricular cardiomyocytes during their development as well as during cardiac diseases.

Návaznosti

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, Markéta BÉBAROVÁ a Jiří ŠIMURDA. Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte. In 47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology. 2023.

@proceedings{2334065,
   author = {Pásek, Michal and Bébarová, Markéta and Šimurda, Jiří},
   booktitle = {47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
   keywords = {human ventricular cardiomyocyte; NCX; PMCA},
   language = {eng},
   title = {Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte},
   year = {2023}
}

TY  - CONF
ID  - 2334065
AU  - Pásek, Michal - Bébarová, Markéta - Šimurda, Jiří
PY  - 2023
TI  - Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte
KW  - human ventricular cardiomyocyte
KW  - NCX
KW  - PMCA
N2  - Background: The sarcolemmal Ca2+ efflux pathways, Na+-Ca2+ exchanger (NCX), and Ca2+-ATPase (PMCA), play a crucial role in the regulation of intracellular Ca2+ load and Ca2+ transient. Experimental studies published so far have indicated that the t-tubular fractions of NCX and PMCA (fNaCa,t and fpCa,t) in ventricular myocytes might be lower than 0.3 as well as higher than 0.9. Moreover, the membrane distribution of both transporters appears to vary during development and cardiac diseases. However, the consequences of changes in NCX and PMCA distribution between the t-tubular and surface membranes of human ventricular cardiomyocytes have not yet been elucidated. Methods: We addressed this point by using a mathematical model of the human ventricular myocyte incorporating t-tubules, dyadic spaces, and subsarcolemmal spaces. Effects of various combinations of fNaCa,t and fpCa,t were explored using values between 0.2 and 1 as reported in animal experiments under normal and pathological conditions. For numerical solution, the computational software MATLAB version 7.2 (MathWorks, Natick, MA, USA) was used. Results: Small variations in the duration of action potentials (≤ 2%), but a substantial increase in the peak value of cytosolic Ca2+ transient (up to 18%) were observed in the model when NCX and PMCA were redistributed to the t-tubular or surface membranes. This effect was caused by an increase of Ca2+ load in the sarcoplasmic reticulum due to an increase of Ca2+ concentration in the cytosol (after the termination of Ca2+ transient) in response to the reduced activity of NCX and PMCA under the membrane domain where these transporters predominated. Conclusion: These results indicate that redistribution of both transporters between the t-tubular and surface membranes may contribute to the changes in the inotropic state of human ventricular cardiomyocytes during their development as well as during cardiac diseases.
ER  -

PÁSEK, Michal, Markéta BÉBAROVÁ a Jiří ŠIMURDA. Functional consequences of different distribution of NCX and PMCA between t-tubular and surface membranes in a model of the human ventricular cardiomyocyte. In \textit{47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2023.

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