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Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia

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Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia. / Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A F; Fu, Chi Cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

In: Stem Cell Reports, Vol. 3, No. 2, 12.08.2014, p. 269-281.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Spencer, CI, Baba, S, Nakamura, K, Hua, EA, Sears, MAF, Fu, CC, Zhang, J, Balijepalli, S, Tomoda, K, Hayashi, Y, Lizarraga, P, Wojciak, J, Scheinman, MM, Aalto-Setälä, K, Makielski, JC, January, CT, Healy, KE, Kamp, TJ, Yamanaka, S & Conklin, BR 2014, 'Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia', Stem Cell Reports, vol. 3, no. 2, pp. 269-281. https://doi.org/10.1016/j.stemcr.2014.06.003

APA

Spencer, C. I., Baba, S., Nakamura, K., Hua, E. A., Sears, M. A. F., Fu, C. C., ... Conklin, B. R. (2014). Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia. Stem Cell Reports, 3(2), 269-281. https://doi.org/10.1016/j.stemcr.2014.06.003

Vancouver

Spencer CI, Baba S, Nakamura K, Hua EA, Sears MAF, Fu CC et al. Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia. Stem Cell Reports. 2014 Aug 12;3(2):269-281. https://doi.org/10.1016/j.stemcr.2014.06.003

Author

Spencer, C. Ian ; Baba, Shiro ; Nakamura, Kenta ; Hua, Ethan A. ; Sears, Marie A F ; Fu, Chi Cheng ; Zhang, Jianhua ; Balijepalli, Sadguna ; Tomoda, Kiichiro ; Hayashi, Yohei ; Lizarraga, Paweena ; Wojciak, Julianne ; Scheinman, Melvin M. ; Aalto-Setälä, Katriina ; Makielski, Jonathan C. ; January, Craig T. ; Healy, Kevin E. ; Kamp, Timothy J. ; Yamanaka, Shinya ; Conklin, Bruce R. / Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia. In: Stem Cell Reports. 2014 ; Vol. 3, No. 2. pp. 269-281.

Bibtex - Download

@article{4a14e01ab8194e829680f0d292683943,
title = "Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia",
abstract = "Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+] i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.",
author = "Spencer, {C. Ian} and Shiro Baba and Kenta Nakamura and Hua, {Ethan A.} and Sears, {Marie A F} and Fu, {Chi Cheng} and Jianhua Zhang and Sadguna Balijepalli and Kiichiro Tomoda and Yohei Hayashi and Paweena Lizarraga and Julianne Wojciak and Scheinman, {Melvin M.} and Katriina Aalto-Set{\"a}l{\"a} and Makielski, {Jonathan C.} and January, {Craig T.} and Healy, {Kevin E.} and Kamp, {Timothy J.} and Shinya Yamanaka and Conklin, {Bruce R.}",
year = "2014",
month = "8",
day = "12",
doi = "10.1016/j.stemcr.2014.06.003",
language = "English",
volume = "3",
pages = "269--281",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Elsevier",
number = "2",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia

AU - Spencer, C. Ian

AU - Baba, Shiro

AU - Nakamura, Kenta

AU - Hua, Ethan A.

AU - Sears, Marie A F

AU - Fu, Chi Cheng

AU - Zhang, Jianhua

AU - Balijepalli, Sadguna

AU - Tomoda, Kiichiro

AU - Hayashi, Yohei

AU - Lizarraga, Paweena

AU - Wojciak, Julianne

AU - Scheinman, Melvin M.

AU - Aalto-Setälä, Katriina

AU - Makielski, Jonathan C.

AU - January, Craig T.

AU - Healy, Kevin E.

AU - Kamp, Timothy J.

AU - Yamanaka, Shinya

AU - Conklin, Bruce R.

PY - 2014/8/12

Y1 - 2014/8/12

N2 - Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+] i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

AB - Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+] i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

UR - http://www.scopus.com/inward/record.url?scp=84924219943&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2014.06.003

DO - 10.1016/j.stemcr.2014.06.003

M3 - Article

VL - 3

SP - 269

EP - 281

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 2

ER -