Zhang, Xiao-Hua, Saric, Tomo, Mehrjardi, Narges Zare, Hamad, Sarkawt ORCID: 0000-0002-5155-9467 and Morad, Martin (2019). Acid-Sensitive Ion Channels Are Expressed in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cells Dev., 28 (14). S. 920 - 933. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-8534

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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. In this study, we tested for expression of acid sensing ion channels (ASICs) 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 E-Na, was suppressed by 5 mu M 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 decreased in 100 days postdifferentiation hiPSC cultures. Hyperacidification (pH 5 and 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 current nor its protein was detected in rat adult cardiomyocytes, but hyperacidification 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zhang, Xiao-HuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saric, TomoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehrjardi, Narges ZareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamad, SarkawtUNSPECIFIEDorcid.org/0000-0002-5155-9467UNSPECIFIED
Morad, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-135139
DOI: 10.1089/scd.2018.0234
Journal or Publication Title: Stem Cells Dev.
Volume: 28
Number: 14
Page Range: S. 920 - 933
Date: 2019
Publisher: MARY ANN LIEBERT, INC
Place of Publication: NEW ROCHELLE
ISSN: 1557-8534
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CA2+; PHARMACOLOGY; INHIBITORS; MECHANISM; RECEPTORMultiple languages
Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; TransplantationMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13513

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