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 and Jiří ŠIMURDA

Basic information

Original name

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

Authors

PÁSEK, Michal (203 Czech Republic, guarantor, belonging to the institution), Markéta BÉBAROVÁ (203 Czech Republic, belonging to the institution) and Jiří ŠIMURDA (203 Czech Republic)

Edition

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

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Denmark

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14110/23:00134666

Organization unit

Faculty of Medicine

Keywords in English

human ventricular cardiomyocyte; NCX; PMCA

Abstract

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.

Links

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

Citovat

PÁSEK, Michal, Markéta BÉBAROVÁ and 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 and 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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