title: Possible effects of inhibition of IKr and IKs on field-potential waveforms in the human iPS cell-derived cardiomyocytes sheet.
abstract: In order to investigate how IKr and IKs inhibitions affect waveforms of the field potential in the human iPS cell-derived cardiomyocytes sheet, we analyzed the effects of E-4031 and chromanol 293B on the maximum upslope and peak amplitude of its second wave (n = 7 for each drug). E-4031 in 10-100 nM as well as chromanol 293B in 3-30 μM prolonged the field-potential duration, whereas E-4031 decreased the upslope in 10-100 nM and amplitude at 100 nM, which was not observed by chromanol 293B. Thus, the decrease of the upslope can be used as a supplemental marker of drug-induced IKr inhibition.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Japan; Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd., Japan; Division of Pharmacology, National Institute of Health Sciences, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuo
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekino
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Japan. Electronic address: atsushi.sugiyama@med.toho-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D002839:Chromans; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D013449:Sulfonamides; C063968:E 4031; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane
keywords: Field potential; I(Kr); iPS cell-derived cardiomyocytes