Characterization of Neurons Derived from a Human Induced Pluripotent Stem Cell Line Using Patch‐Clamp Electrophysiology

Abstract

Neuropharmacological studies using animal‐derived tissues are not always directly translatable to humans, and the occurrence of discrepancies can be difficult to predict. Sources of human neurons have been limited in the past, but developments in stem cell science are now providing new opportunities to generate human neurons from stem cells. iCell neurons are derived from a human induced pluripotent stem cell (hIPSC) line and may have the potential to replace animal neurons in neuropharmacological studies. Here, we have explored the neurophysiological and neuropharmacological properties of iCell neurons using immunocytochemistry and single‐cell patch‐clamp techniques.Whole cell recordings were obtained from iCell neurons cultured for up to 4 months in vitro. Functional expression of voltage‐gated sodium and potassium ion channels, as well as ligand‐gated GABAA, glutamate, NMDA, AMPA, kainate and glycine receptors was determined. Spontaneous and evoked action potentials were inhibited by the sodium channel blocker tetrodotoxin, and spontaneous activity levels increased over time in culture. Immunocytochemical analysis revealed a corresponding increase in neurite density over time. iCell neurons therefore appear to have several important functional properties consistent with human neurons and might be a viable alternative to animal neurons in drug studies.Research support was provided by Cellular Dynamics International and the Department of Physiology and Pharmacology at the University of the Pacific.