Generating an Improved iPSC-CM Model System for Studying the Effects of Cav1.2 Mutations

Abstract

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) are a useful model system for studying cardiac diseases such as long QT syndrome (LQTS), a condition in which repolarization of the heart is stalled resulting in life-threatening arrhythmias. Mutations within the calcium channel Cav1.2 are known to cause LQTS, making iPSC-CMs a useful model system for studying the mechanism of this form of LQTS. However, iPSC-CMs are often immature and don’t mimic adult heart cells in several ways, as their complement of ion channels seems to differ from adult CMs. Consequently, we found iPSC-CMs and adult CMs responses to calcium channel blockers such as verapamil, to not be comparable. Using optical mapping, we demonstrate that a hormone cocktail treatment which has been shown to improve maturation of iPSC-CM, provides a partial rescue of the iPSC-CM verapamil response. We therefore identified a method for improving the usefulness of iPSC-CMs in studying LQTS.