Real-time simulation of IK1 in cardiomyocytes derived from human induced pluripotent stem cells
Publikation: Beitrag in Buch/Konferenzbericht/Sammelband/Gutachten › Beitrag in Konferenzband › Beigetragen › Begutachtung
Beitragende
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
Originalsprache | Englisch |
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Titel | Computing in Cardiology Conference 2015, CinC 2015 |
Redakteure/-innen | Alan Murray |
Herausgeber (Verlag) | IEEE Computer Society, Washington |
Seiten | 157-160 |
Seitenumfang | 4 |
ISBN (elektronisch) | 9781509006854 |
Publikationsstatus | Veröffentlicht - 16 Feb. 2015 |
Peer-Review-Status | Ja |
Publikationsreihe
Reihe | Computing in Cardiology |
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Band | 42 |
ISSN | 0276-6574 |
Konferenz
Titel | 42nd Computing in Cardiology Conference |
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Kurztitel | CinC 2015 |
Veranstaltungsnummer | 42 |
Dauer | 6 - 9 September 2015 |
Webseite | |
Bekanntheitsgrad | Internationale Veranstaltung |
Ort | University of Nice |
Stadt | Nice |
Land | Frankreich |