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Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes

Tutkimustuotosvertaisarvioitu

Standard

Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes. / Björk, Susann; Ojala, Elina A.; Nordström, Tommy; Ahola, Antti; Liljeström, Mikko; Hyttinen, Jari; Kankuri, Esko; Mervaala, Eero.

julkaisussa: Frontiers in Physiology, Vuosikerta 8, Nro NOV, 884, 02.11.2017.

Tutkimustuotosvertaisarvioitu

Harvard

Björk, S, Ojala, EA, Nordström, T, Ahola, A, Liljeström, M, Hyttinen, J, Kankuri, E & Mervaala, E 2017, 'Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes', Frontiers in Physiology, Vuosikerta. 8, Nro NOV, 884. https://doi.org/10.3389/fphys.2017.00884

APA

Björk, S., Ojala, E. A., Nordström, T., Ahola, A., Liljeström, M., Hyttinen, J., ... Mervaala, E. (2017). Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes. Frontiers in Physiology, 8(NOV), [884]. https://doi.org/10.3389/fphys.2017.00884

Vancouver

Björk S, Ojala EA, Nordström T, Ahola A, Liljeström M, Hyttinen J et al. Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes. Frontiers in Physiology. 2017 marras 2;8(NOV). 884. https://doi.org/10.3389/fphys.2017.00884

Author

Björk, Susann ; Ojala, Elina A. ; Nordström, Tommy ; Ahola, Antti ; Liljeström, Mikko ; Hyttinen, Jari ; Kankuri, Esko ; Mervaala, Eero. / Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes. Julkaisussa: Frontiers in Physiology. 2017 ; Vuosikerta 8, Nro NOV.

Bibtex - Lataa

@article{747f5fb64cc2436fbece35d880ed8444,
title = "Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes",
abstract = "Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.",
keywords = "Arrhythmia, Cardiac electrophysiology, Contractile motion, HERG, Human iPSC-derived cardiomyocytes, Optical action potential, Optogenetics, Safety pharmacology",
author = "Susann Bj{\"o}rk and Ojala, {Elina A.} and Tommy Nordstr{\"o}m and Antti Ahola and Mikko Liljestr{\"o}m and Jari Hyttinen and Esko Kankuri and Eero Mervaala",
year = "2017",
month = "11",
day = "2",
doi = "10.3389/fphys.2017.00884",
language = "English",
volume = "8",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers",
number = "NOV",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes

AU - Björk, Susann

AU - Ojala, Elina A.

AU - Nordström, Tommy

AU - Ahola, Antti

AU - Liljeström, Mikko

AU - Hyttinen, Jari

AU - Kankuri, Esko

AU - Mervaala, Eero

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.

AB - Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.

KW - Arrhythmia

KW - Cardiac electrophysiology

KW - Contractile motion

KW - HERG

KW - Human iPSC-derived cardiomyocytes

KW - Optical action potential

KW - Optogenetics

KW - Safety pharmacology

U2 - 10.3389/fphys.2017.00884

DO - 10.3389/fphys.2017.00884

M3 - Article

VL - 8

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - NOV

M1 - 884

ER -