Functional consequences of changes in the distribution of Ca2+ extrusion pathways between t-tubular and surface membranes in a model of human ventricular cardiomyocyte
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
38960316
DOI
10.1016/j.yjmcc.2024.06.010
PII: S0022-2828(24)00107-X
Knihovny.cz E-zdroje
- Klíčová slova
- Calcium ATPase, Calcium cycling, Human ventricular cell model, Membrane protein distribution, NCX, PMCA, Sodium‑calcium exchanger, T-tubules,
- MeSH
- akční potenciály MeSH
- biologické modely MeSH
- buněčná membrána metabolismus MeSH
- kardiomyocyty * metabolismus MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- pumpa pro výměnu sodíku a vápníku * metabolismus MeSH
- sarkolema * metabolismus MeSH
- srdeční komory * metabolismus MeSH
- vápník * metabolismus MeSH
- vápníková signalizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- pumpa pro výměnu sodíku a vápníku * MeSH
- vápník * MeSH
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 membrane of ventricular cardiomyocytes varies between species and is not clear in human. 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.
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