Stem Cells Dev. 2019 May 23. doi: 10.1089/scd.2018.0234. [Epub ahead of print]

Acid Sensitive Ion channels are expressed in human induced pluripotent stem cell-derived cardiomyocytes.

Zhang XH¹, Saric T², Mehrjardi NZ³, Hamad S⁴, Morad M⁵.

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are potential sources for cardiac regeneration and drug development. hiPSC-CMs express all the cardiac ion channels and the unique cardiac Ca2+-signaling phenotype. Here we tested for expression of acid sensing ion channels (ASIC) in spontaneously beating cardiomyocytes derived from three different hiPSC lines (IMR-90, iPSC-K3 and Ukki011-A). Rapid application of solutions buffered at pH 6.7, 6.0, or 5.0 triggered rapidly activating and slowly inactivating voltage-independent inward current that reversed at voltages positive to ENa, was suppressed by 5µM amiloride and withdrawal of [Na+]o , like neuronal ASIC currents. ASIC currents were expressed at much lower percentages and densities in undifferentiated hiPSC, and in dermal fibroblasts. ASIC1 mRNA and protein were measured in first 60 days but not 100-days post-differentiation hiPSC cultures. Hyper-acidification (pH5-6) also triggered large Ca2+ transients in intact hiPSC-CMs that were neither ruthenium red nor amiloride-sensitive, but were absent in whole cell-clamped hiPSC-CMs. Neither ASIC1 currents nor its protein were detected in rat adult cardiomyocytes, but hyper-acidification did activate smaller and slowly activating currents with drug sensitivity similar to TRPV channels. Considering ASIC expression in developing but not adult myocardium, a role in heart development is likely.