Application of human induced pluripotent stem cell-derived cardiomyocytes sheets with microelectrode array system to estimate antiarrhythmic properties of multi-ion channel blockers

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 a...

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Main Authors: Hiroko Izumi-Nakaseko (Author), Mihoko Hagiwara-Nagasawa (Author), Atsuhiko T. Naito (Author), Ai Goto (Author), Koki Chiba (Author), Yuko Sekino (Author), Yasunari Kanda (Author), Atsushi Sugiyama (Author)
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Published: Elsevier, 2018-08-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Hiroko Izumi-Nakaseko  |e author 
700 1 0 |a Mihoko Hagiwara-Nagasawa  |e author 
700 1 0 |a Atsuhiko T. Naito  |e author 
700 1 0 |a Ai Goto  |e author 
700 1 0 |a Koki Chiba  |e author 
700 1 0 |a Yuko Sekino  |e author 
700 1 0 |a Yasunari Kanda  |e author 
700 1 0 |a Atsushi Sugiyama  |e author 
245 0 0 |a Application of human induced pluripotent stem cell-derived cardiomyocytes sheets with microelectrode array system to estimate antiarrhythmic properties of multi-ion channel blockers 
260 |b Elsevier,   |c 2018-08-01T00:00:00Z. 
500 |a 1347-8613 
500 |a 10.1016/j.jphs.2018.07.011 
520 |a 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-à-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. Keywords: Human induced pluripotent stem cell-derived cardiomyocytes, Post repolarization refractoriness, Multichannel blocker, Antiarrhythmic property 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Journal of Pharmacological Sciences, Vol 137, Iss 4, Pp 372-378 (2018) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1347861318301312 
787 0 |n https://doaj.org/toc/1347-8613 
856 4 1 |u https://doaj.org/article/5f801f9b043947e7b986f49b18cd13e1  |z Connect to this object online.