Commercially Available Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Another Piece in Our Tool Box, but Not a Swiss Army Knife Yet.

Abstract

KCNJ2 encodes the pore-forming α-subunit of the Kir2.1 inward-rectifier potassium channel, the main determinant of the current (I K1 ), which is responsible for the final repolarization phase of the ventricular action potential, as well as a stable resting membrane potential in the working myocardium. Variants in the KCNJ2 gene have been associated with familial atrial fibrillation (gain of function), short-QT syndrome (gain of function), catecholaminergic polymorphic ventricular tachycardia; loss of function), as well as the Andersen–Tawil syndrome (ATS; loss of function). ATS is a rare hereditary multisystem disorder leading to periodic paralysis, dysmorphic features, and ventricular arrhythmias. Penetrance of the disease is extremely variable, and not all patients present with the full triad of symptoms. Regarding the cardiac phenotype, these patients present with frequent polymorphic ventricular contractions and bidirectional ventricular tachycardia. Typically, these arrhythmias are present at rest and disappear during exercise. This is an important differentiation from catecholaminergic polymorphic ventricular tachycardia, which also presents with bidirectional tachycardia, but typically during catecholaminergic stimulation or exercise. ATS patients frequently show prominent U waves in the ECG, and some also show prolongation of the corrected QT interval. Although QT prolongation is not a typical sign, ATS was classified as LQTS-subtype (LQT7).