title: Human pluripotent stem cell-derived cardiomyocytes: response to TTX and lidocain reveals strong cell to cell variability.
abstract: Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution.
authors.affiliation: Institute for Neurophysiology, University of Cologne, Germany.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Sheng
authors.forename: Michael
authors.initials: M
authors.lastname: Reppel
authors.forename: Filomain
authors.initials: F
authors.lastname: Nguemo
authors.forename: Farooq Ibrahem
authors.initials: FI
authors.lastname: Mohammad
authors.forename: Alexey
authors.initials: A
authors.lastname: Kuzmenkin
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Kurt
authors.initials: K
authors.lastname: Pfannkuche
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D007473:Ion Channels; D018721:Muscarinic Agonists; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D008012:Lidocaine