Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cells. 2022 Aug 5;11(15):2424. doi: 10.3390/cells11152424.
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.
NCX 在人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）中的生理重要性尚未得到很好的描述，但可能取决于电流的相对强度，与成人心肌细胞相比，以及参与 Ca2+ 外排的蛋白质的精确空间排列。在这里，我们确定了在工程心脏组织（EHT）中培养的 hiPSC-CMs 中的 NCX 电流及其对动作电位和力的贡献。将结果与来自大鼠和人心室组织的数据进行比较。hiPSC-CMs 中的 NCX 电流大于从人心室分离的心室肌细胞（分别为人心室和 EHT 的 1.3 ± 0.2 pA/pF 和 3.2 ± 0.2 pA/pF，p < 0.05）。SEA0400（10 µM）显著缩短了 EHT（缩短 26.6 ± 5%，p < 0.05）和大鼠心室组织（缩短 10.7 ± 1.6%，p < 0.05）的 APD90。人心室制剂的缩短很小，与时间匹配的对照（TMC）无差异（p > 0.05）。NCX 阻断在大鼠心室（增加 31 ± 5.4%，p < 0.05）和 EHT（增加 20.8 ± 3.9%，p < 0.05）中增加了力，但在人心室制剂中没有增加。总之，hiPSC-CMs 具有不小于人心室组织的 NCX 电流。强大的 NCX 阻断诱导的 APD 缩短和正性肌力作用使 EHT 成为一种有吸引力的药理学模型。
Zotero 插件
