Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue

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Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue. / Ismaili, Djemail; Gurr, Katrin; Horváth, András; Yuan, Lei; Lemoine, Marc D; Schulz, Carl; Sani, Jascha; Petersen, Johannes; Reichenspurner, Hermann; Kirchhof, Paulus; Jespersen, Thomas; Eschenhagen, Thomas; Hansen, Arne; Koivumäki, Jussi T; Christ, Torsten.

in: CELLS-BASEL, Jahrgang 11, Nr. 15, 2424, 05.08.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{fd5742a6d13b43cbb40f123bdaa294a0,
title = "Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue",
abstract = "The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.",
keywords = "Action Potentials, Adult, Animals, Heart Ventricles/metabolism, Humans, Induced Pluripotent Stem Cells/metabolism, Myocytes, Cardiac/metabolism, Rats, Sodium-Calcium Exchanger/metabolism",
author = "Djemail Ismaili and Katrin Gurr and Andr{\'a}s Horv{\'a}th and Lei Yuan and Lemoine, {Marc D} and Carl Schulz and Jascha Sani and Johannes Petersen and Hermann Reichenspurner and Paulus Kirchhof and Thomas Jespersen and Thomas Eschenhagen and Arne Hansen and Koivum{\"a}ki, {Jussi T} and Torsten Christ",
year = "2022",
month = aug,
day = "5",
doi = "10.3390/cells11152424",
language = "English",
volume = "11",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "15",

}

RIS

TY - JOUR

T1 - Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue

AU - Ismaili, Djemail

AU - Gurr, Katrin

AU - Horváth, András

AU - Yuan, Lei

AU - Lemoine, Marc D

AU - Schulz, Carl

AU - Sani, Jascha

AU - Petersen, Johannes

AU - Reichenspurner, Hermann

AU - Kirchhof, Paulus

AU - Jespersen, Thomas

AU - Eschenhagen, Thomas

AU - Hansen, Arne

AU - Koivumäki, Jussi T

AU - Christ, Torsten

PY - 2022/8/5

Y1 - 2022/8/5

N2 - The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.

AB - The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.

KW - Action Potentials

KW - Adult

KW - Animals

KW - Heart Ventricles/metabolism

KW - Humans

KW - Induced Pluripotent Stem Cells/metabolism

KW - Myocytes, Cardiac/metabolism

KW - Rats

KW - Sodium-Calcium Exchanger/metabolism

U2 - 10.3390/cells11152424

DO - 10.3390/cells11152424

M3 - SCORING: Journal article

C2 - 35954268

VL - 11

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 15

M1 - 2424

ER -