Functional consequences of changes in the distribution of Ca2+ extrusion pathways between t-tubular and surface membranes in a model of human ventricular cardiomyocyte

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388998%3A_____%2F24%3A00587422" target="_blank" >RIV/61388998:_____/24:00587422 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/24:00080268 RIV/00216224:14110/24:00139948

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S002228282400107X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S002228282400107X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.yjmcc.2024.06.010" target="_blank" >10.1016/j.yjmcc.2024.06.010</a>

Result language

angličtina

Original language name

Functional consequences of changes in the distribution of Ca2+ extrusion pathways between t-tubular and surface membranes in a model of human ventricular cardiomyocyte

Original language description

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 in cardiomyocytes. The distribution of these pathways between the t-tubular and surface membranes of ventricular cardiomyocytes varies between species and is not clear in humans. Moreover, several studies suggest that this distribution changes during the development and heart diseases. However, the consequences of NCX and PMCA redistribution in human ventricular cardiomyocytes have not yet been elucidated. In this study, we aimed to address 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 t-tubular fractions of NCX and PMCA were explored, using values between 0.2 and 1 as reported in animal experiments under normal and pathological conditions. Small variations in the action potential duration (≤ 2%), but significant changes in the peak value of cytosolic Ca2+ transient (up to 17%) were observed at stimulation frequencies corresponding to the human heart rate at rest and during activity. The analysis of model results revealed that the changes in Ca2+ transient induced by redistribution of NCX and PMCA were mainly caused by alterations in Ca2+ concentrations in the subsarcolemmal spaces and cytosol during the diastolic phase of the stimulation cycle. The results suggest that redistribution of both transporters between the t-tubular and surface membranes contributes to changes in contractility in human ventricular cardiomyocytes during their development and heart disease and may promote arrhythmogenesis.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10610 - Biophysics

Project

<a href="/en/project/NU22-02-00348" target="_blank" >NU22-02-00348: Functional assessment of genetic variants in clinically “true” cases of idiopathic ventricular fibrillation: in vitro and in silico modelling to reveal the arrhythmogenic mechanism</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular and Cellular Cardiology

ISSN

0022-2828

e-ISSN

1095-8584

Volume of the periodical

193

Issue of the periodical within the volume

August

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

113-124

UT code for WoS article

001266902200001

EID of the result in the Scopus database

2-s2.0-85197577849