Numerical Simulations Indicate IK1 Dynamic Clamp Can Unveil the Phenotype of Cardiomyocytes Derived from Induced Pluripotent Stem Cells

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are a virtually endless source of human cardiomyocytes, considerably used in vitro models to test drug toxicity. These cells express the major cardiac markers and ion channels, but they also result in a mix of incompletely mature cardiac cells that can be classified as atrial-like and ventricular-like cardiomyocytes. One of the most popular manipulations used to push towards more adult cardiac phenotypes is the dynamic clamp technique, based on virtual inward - rectifier potassium current $(I_{K1})$ injection. In this exploratory in silico study, six different $I_{K1}$ expressions have been virtually analyzed to classify $hiPSC$-CM phenotypes. Starting from the resulting action potential morphologies, we defined a mathematical criterion to estimate the efficacy of the injected $I_{K1}$ current in terms of the threshold percentage of the current density required to obtain an $hiPSC$-CM physiological response. $It$ was found that atrial $I_{K1}$ formulations are more reliable than ventricular ones, with the Koivumäki $I_{K1}$ formulation being the most appropriate since it requires the minimal current density to be injected.