Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue
Standard
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, Vol. 11, No. 15, 2424, 05.08.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
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 -