Possible effects of inhibition of IKr and IKs on field-potential waveforms in the human iPS cell-derived cardiomyocytes sheet

J Pharmacol Sci. 2015 Jun;128(2):92-5. doi: 10.1016/j.jphs.2015.05.004. Epub 2015 May 23.

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.

Keywords: Field potential; I(Kr); iPS cell-derived cardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Arrhythmia Agents / pharmacology*
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Chromans / pharmacology*
  • Evoked Potentials / drug effects*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Piperidines / pharmacology*
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / metabolism*
  • Pyridines / pharmacology*
  • Sulfonamides / pharmacology*

Substances

  • Anti-Arrhythmia Agents
  • Chromans
  • Piperidines
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyridines
  • Sulfonamides
  • E 4031
  • 6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane