Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 137, Issue 4, Pages 372-378Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2018.07.011
Keywords
Human induced pluripotent stem cell-derived cardiomyocytes; Post repolarization refractoriness; Multichannel blocker; Antiarrhythmic property
Categories
Funding
- Toho University Graduate School of Medicine [28-24]
- JSPS KAKENHI [17K08608, 16K08559]
- Japan Agency for Medical Research and Development (AMED) [15mk0104053h0101, 16mk0104027j0002, 17mk0104027j0003, 18mk0104117j001, JP18am0101122]
- Initiative for Realizing Diversity in the Research Environment
- Grants-in-Aid for Scientific Research [17K08608] Funding Source: KAKEN
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We examined electrophysiological indices of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets in order to quantitatively estimate Na+, K+ and Ca2+ channel blocking actions of bepridil and amiodarone using microelectrode array system in comparison with that of E-4031. We analyzed the field potential duration, effective refractory period, current threshold and conduction property using a programmed electrical stimulation protocol to obtain the post repolarization refractoriness and coefficient a of the relationship between the pacing cycle length and field potential duration. Electropharmacological profile of each drug was successfully characterized; namely, 1) the changes in the current threshold and conduction property provided basic information of Na+ channel blocking kinetics, 2) the relationship between pacing cycle length and field potential duration reflected drug-induced inhibition of human ether-a-go-go-related gene (hERG) K+ channel, 3) the post repolarization refractoriness indicated the relative contribution of these drugs to Na+ and K+ channel blockade, and 4) L-type Ca2+ channel blocking action was more obvious in the field potential waveform of the hiPSC-CMs sheets than that expected in the electrocardiogram in humans. Thus, this information may help to better utilize the hiPSC-CMs sheets for grasping the properties and net effects of drug-induced Na+, Ca2+ and K+ channel blockade. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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