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Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations

Tutkimustuotosvertaisarvioitu

Standard

Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations. / Kiviaho, Anna L.; Ahola, Antti; Larsson, Kim; Penttinen, Kirsi; Swan, Heikki; Pekkanen-Mattila, Mari; Venäläinen, Henna; Paavola, Kiti; Hyttinen, Jari; Aalto-Setälä, Katriina.

julkaisussa: IJC Heart and Vasculature, Vuosikerta 8, 01.09.2015, s. 19-31.

Tutkimustuotosvertaisarvioitu

Harvard

Kiviaho, AL, Ahola, A, Larsson, K, Penttinen, K, Swan, H, Pekkanen-Mattila, M, Venäläinen, H, Paavola, K, Hyttinen, J & Aalto-Setälä, K 2015, 'Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations', IJC Heart and Vasculature, Vuosikerta. 8, Sivut 19-31. https://doi.org/10.1016/j.ijcha.2015.04.008

APA

Kiviaho, A. L., Ahola, A., Larsson, K., Penttinen, K., Swan, H., Pekkanen-Mattila, M., ... Aalto-Setälä, K. (2015). Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations. IJC Heart and Vasculature, 8, 19-31. https://doi.org/10.1016/j.ijcha.2015.04.008

Vancouver

Kiviaho AL, Ahola A, Larsson K, Penttinen K, Swan H, Pekkanen-Mattila M et al. Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations. IJC Heart and Vasculature. 2015 syys 1;8:19-31. https://doi.org/10.1016/j.ijcha.2015.04.008

Author

Kiviaho, Anna L. ; Ahola, Antti ; Larsson, Kim ; Penttinen, Kirsi ; Swan, Heikki ; Pekkanen-Mattila, Mari ; Venäläinen, Henna ; Paavola, Kiti ; Hyttinen, Jari ; Aalto-Setälä, Katriina. / Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations. Julkaisussa: IJC Heart and Vasculature. 2015 ; Vuosikerta 8. Sivut 19-31.

Bibtex - Lataa

@article{9b2db21f13524db3b163340f3e79cc55,
title = "Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations",
abstract = "Background: Long QT syndrome (LQTS) is associated with increased risk of ventricular arrhythmias and cardiac arrest. LQTS type 1 (LQT1), the most prevalent subtype of LQTS, is caused by defects of slow delayed rectifier potassium current (IKs) that lead to abnormal cardiac repolarization. Here we used pluripotent stem cell (iPSC)-technology to investigate both the electrophysiological and also for the first time the mechanical beating behavior of genetically defined, LQT1 specific cardiomyocytes (CMs) carrying different mutations. Methods: We established in vitro models for LQT1 caused by two mutations (G589D or ivs7-2A>G). LQT1 specific CMs were derived from patient specific iPSCs and characterized for their electrophysiology using a current clamp and Ca2+-imaging. Their mechanical beating characteristics were analyzed with video-image analysis method. Results and conclusions: Both LQT1-CM-types showed prolonged repolarization, but only those with G589D presented early after-depolarizations at baseline. Increased amounts of abnormal Ca2+ transients were detected in both types of LQT1-CMs. Surprisingly, also the mechanical beating behavior demonstrated clear abnormalities and additionally the abnormalities were different with the two mutations: prolonged contraction was seen in G589D-CMs while impaired relaxation was observed in ivs7-2A>G-CMs.The CMs carrying two different LQT1 specific mutations (G589D or ivs7-2A>G) presented clear differences in their electrical properties as well as in their mechanical beating behavior. Results from different methods correlated well with each other suggesting that simply mechanical beating behavior of CMs could be used for screening of diseased CMs and possibly for diagnostic purposes in the future.",
keywords = "Arrhythmia, Calcium imaging, Digital image correlation, Induced pluripotent stem cell, Long QT syndrome, Patch clamp",
author = "Kiviaho, {Anna L.} and Antti Ahola and Kim Larsson and Kirsi Penttinen and Heikki Swan and Mari Pekkanen-Mattila and Henna Ven{\"a}l{\"a}inen and Kiti Paavola and Jari Hyttinen and Katriina Aalto-Set{\"a}l{\"a}",
note = "EXT={"}Penttinen, Kirsi{"}",
year = "2015",
month = "9",
day = "1",
doi = "10.1016/j.ijcha.2015.04.008",
language = "English",
volume = "8",
pages = "19--31",
journal = "IJC Heart and Vasculature",
issn = "2352-9067",
publisher = "Elsevier BV",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations

AU - Kiviaho, Anna L.

AU - Ahola, Antti

AU - Larsson, Kim

AU - Penttinen, Kirsi

AU - Swan, Heikki

AU - Pekkanen-Mattila, Mari

AU - Venäläinen, Henna

AU - Paavola, Kiti

AU - Hyttinen, Jari

AU - Aalto-Setälä, Katriina

N1 - EXT="Penttinen, Kirsi"

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background: Long QT syndrome (LQTS) is associated with increased risk of ventricular arrhythmias and cardiac arrest. LQTS type 1 (LQT1), the most prevalent subtype of LQTS, is caused by defects of slow delayed rectifier potassium current (IKs) that lead to abnormal cardiac repolarization. Here we used pluripotent stem cell (iPSC)-technology to investigate both the electrophysiological and also for the first time the mechanical beating behavior of genetically defined, LQT1 specific cardiomyocytes (CMs) carrying different mutations. Methods: We established in vitro models for LQT1 caused by two mutations (G589D or ivs7-2A>G). LQT1 specific CMs were derived from patient specific iPSCs and characterized for their electrophysiology using a current clamp and Ca2+-imaging. Their mechanical beating characteristics were analyzed with video-image analysis method. Results and conclusions: Both LQT1-CM-types showed prolonged repolarization, but only those with G589D presented early after-depolarizations at baseline. Increased amounts of abnormal Ca2+ transients were detected in both types of LQT1-CMs. Surprisingly, also the mechanical beating behavior demonstrated clear abnormalities and additionally the abnormalities were different with the two mutations: prolonged contraction was seen in G589D-CMs while impaired relaxation was observed in ivs7-2A>G-CMs.The CMs carrying two different LQT1 specific mutations (G589D or ivs7-2A>G) presented clear differences in their electrical properties as well as in their mechanical beating behavior. Results from different methods correlated well with each other suggesting that simply mechanical beating behavior of CMs could be used for screening of diseased CMs and possibly for diagnostic purposes in the future.

AB - Background: Long QT syndrome (LQTS) is associated with increased risk of ventricular arrhythmias and cardiac arrest. LQTS type 1 (LQT1), the most prevalent subtype of LQTS, is caused by defects of slow delayed rectifier potassium current (IKs) that lead to abnormal cardiac repolarization. Here we used pluripotent stem cell (iPSC)-technology to investigate both the electrophysiological and also for the first time the mechanical beating behavior of genetically defined, LQT1 specific cardiomyocytes (CMs) carrying different mutations. Methods: We established in vitro models for LQT1 caused by two mutations (G589D or ivs7-2A>G). LQT1 specific CMs were derived from patient specific iPSCs and characterized for their electrophysiology using a current clamp and Ca2+-imaging. Their mechanical beating characteristics were analyzed with video-image analysis method. Results and conclusions: Both LQT1-CM-types showed prolonged repolarization, but only those with G589D presented early after-depolarizations at baseline. Increased amounts of abnormal Ca2+ transients were detected in both types of LQT1-CMs. Surprisingly, also the mechanical beating behavior demonstrated clear abnormalities and additionally the abnormalities were different with the two mutations: prolonged contraction was seen in G589D-CMs while impaired relaxation was observed in ivs7-2A>G-CMs.The CMs carrying two different LQT1 specific mutations (G589D or ivs7-2A>G) presented clear differences in their electrical properties as well as in their mechanical beating behavior. Results from different methods correlated well with each other suggesting that simply mechanical beating behavior of CMs could be used for screening of diseased CMs and possibly for diagnostic purposes in the future.

KW - Arrhythmia

KW - Calcium imaging

KW - Digital image correlation

KW - Induced pluripotent stem cell

KW - Long QT syndrome

KW - Patch clamp

U2 - 10.1016/j.ijcha.2015.04.008

DO - 10.1016/j.ijcha.2015.04.008

M3 - Article

VL - 8

SP - 19

EP - 31

JO - IJC Heart and Vasculature

JF - IJC Heart and Vasculature

SN - 2352-9067

ER -