Dynamic Current Clamp Experiments Define the Functional Roles of I_K1 and I_to,f in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

Abstract

The transient outward potassium current (Ito) plays a key, albeit incompletely defined, role in cardiomyocyte physiology and pathophysiology.

Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

“…In case of an I K1 with a strong Kir2.1-like rectification, like the I K1 of Meijer van Putten et al [ 5 ] or Rocchetti et al [ 15 ], and also that of Marrus et al [ 58 ], the I K1 at the AP plateau level is negligible. With the more atrial-like I K1 of Bett et al [ 14 ], which is used in the commercially available Cybercyte dynamic clamp system [ 59 ], the I K1 at the plateau level is no longer negligible and shortens the AP of both model cells dramatically ( Figure 9 A,B).…”

“…In their “hiPSC-CMs with ventricular-like APs”, Rocchetti et al [ 15 ] observed statistically significant changes in diastolic potential, APD 50 , APD 90 , and V max upon I K1 injection, as shown in their Figure S11, but the error bars suggest that the decrease in variability of APD 50 and APD 90 is as moderate as in our ventricular-like CTRL hiPSC-CMs. A comprehensive dynamic clamp study on hiPSC-CMs by Marrus et al [ 58 ], which has only been published in preprint form, also shows a moderate decrease in variability of APD 90 upon I K1 injection.…”