Real-time simulation of IK1 in cardiomyocytes derived from human induced pluripotent stem cells

Research output: Contribution to book/conference proceedings/anthology/reportConference contributionContributedpeer-review

Contributors

  • Rosalie M.E.Meijer Van Putten - , University of Amsterdam (Author)
  • Isabella Mengarelli - , University of Amsterdam (Author)
  • Kaomei Guan - , Institute of Pharmacology and Toxicology, University of Göttingen (Author)
  • Jan G. Zegers - , University of Amsterdam (Author)
  • Antoni C.G. Van Ginneken - , University of Amsterdam (Author)
  • Arie O. Verkerk - , University of Amsterdam (Author)
  • Ronald Wilders - , University of Amsterdam (Author)

Abstract

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are widely used in studying basic mechanisms of ventricular arrhythmias. However, their action potential profile-and thereby the profile of individual ionic currents active during that action potential-differs substantially from that of native human cardiomyocytes, which is largely due to an almost negligible expression of the inward rectifier potassium current (IK1). We attempted to 'normalize' the action potential profile of our hiPSC-CMs through real-time simulation of the lacking IK1 in the dynamic clamp configuration of the perforated patch clamp technique, which allows the injection of a voltage-dependent in silico IK1. Without injection of IK1, our hiPSC-CMs showed nodal-like spontaneous beating, but injection of an in silico IK1 unmasked their ventricular-like nature. Proarrhythmic action potential changes were observed upon real-time simulation of both loss-of-function and gain-of-function mutations in IK1, as associated with Andersen-Tawil syndrome type 1 and short QT syndrome type 3, respectively. We conclude that injection of in silico IK1 makes the hiPSC-CM a more reliable model for investigating mechanisms underlying ventricular arrhythmias.

Details

Original languageEnglish
Title of host publicationComputing in Cardiology Conference 2015, CinC 2015
EditorsAlan Murray
PublisherIEEE Computer Society, Washington
Pages157-160
Number of pages4
ISBN (electronic)9781509006854
Publication statusPublished - 16 Feb 2015
Peer-reviewedYes

Publication series

SeriesComputing in Cardiology
Volume42
ISSN0276-6574

Conference

Title42nd Computing in Cardiology Conference
Abbreviated titleCinC 2015
Conference number42
Duration6 - 9 September 2015
Website
Degree of recognitionInternational event
LocationUniversity of Nice
CityNice
CountryFrance