Component Currents of Cardiac Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells

Abstract

Cardiac myocytes derived from human induced pluripotent stem cells (h-iPSCD cardiac myocytes) have been proposed to be useful for cardiac repair, drug safety design and testing, clinical diagnosis and research. However, this particular preparation was only published within the past two years. As a result, we know very little about these artificially created myocytes. We currently lack much of the basic information and the tools required to bring the promise of this approach to fruition. In this study we examine the basic component currents for kinetic clues as to the molecular identity of some of the major components. The normal complement of cardiac currents is found in these cells such as the sodium, calcium, transient outward and delayed rectifier currents. Of particular interest for this study is the inactivation and recovery behavior of the transient outward currents and the calcium currents.The transient outward currents had bi-exponential inactivation including a fast component consistent with Kv4.2/4.3 and a slower “pedestal” component consistent with Kv1.5. The size of this pedestal component was highly variable. The recovery time course and steady-state inactivation indicate at least two distinct inactivation components. This is also consistent with a rapidly recovering Kv4 mediated component and a slower Kv1.5 mediated component.In the mixed population of myocytes there is a calcium current component seen in roughly 30% of cells that that activates in the range of −60 to −50 as opposed to −50 to −40 for the L-type channel in the majority of myocytes. This small component of current also inactivates at a lower threshold than L-type channels and like activation was shifted to the negative range by approximately −10mV. This suggests that “nodal” cells in h-iPSCD cardiac myocytes have a T-type current.