Figure 13
From: New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models
Distinct electrophysiological and ultrastructural characteristics of hiPSC-CMs in comparison with human native/adult ventricular CMs (hV-CMs). Impact of prototypical hiPSC-like ICaL, IK1, and IKr densities, which are 1.5-fold, 0.5-fold, and fourfold in comparison with hV-CM, on the repolarization reserve, simulated as in Ref. 193. The absence of t-tubules in hiPSC-CM results in spatial uncoupling of L-type Ca2 + channel (LTCC) and ryanodine receptors (RyR), as well as irregular distribution of SR Ca2 + handling proteins: RyR, Ca2 + ATPase (SERCA), and its regulatory protein phospholamban (PLN). Furthermore, inositol triphosphate receptors (IP3R) activity is substantially higher in hiPSC-CMs. The panels for were adapted from Ref. 196 CC BY 4.0 (original Fig. 1, http://creativecommons.org/licenses/by/4.0/). (Paci, Michelangelo; Penttinen, Kirsi; Pekkanen-Mattila, Mari; Koivumäki, Jussi T. Arrhythmia Mechanisms in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes. Journal of Cardiovascular Pharmacology77(3):300–316, March 2021. https://doi.org/10.1097/FJC.0000000000000972).
