Cardiac Subtype-Specific Modeling of K_v1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells.

ABSTRACT: The ultrarapid delayed rectifier K⁺ current (I_Kur), mediated by K_v1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of K_v1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout. This model as well as isogenic wild-type control hiPSCs could selectively be differentiated into ventricular or atrial cardiomyocytes at high efficiency, based on th

SUBMITTER: Marczenke M 

PROVIDER: S-EPMC5498524 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature