Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes

Abstract Opening of the mitochondrial permeability transition pore (mPTP) plays a major role in cell death during cardiac ischaemia-reperfusion. Adult isolated rodent cardiomyocytes are valuable cells to study the effect of drugs targeting mPTP. This study investigated whether the use of Ca2+ ionoph...

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Autores principales:	Mathieu Panel, Bijan Ghaleh, Didier Morin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/112b8ebadb8d4885a17d2a0c00dfad04
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spelling	oai:doaj.org-article:112b8ebadb8d4885a17d2a0c00dfad042021-12-02T15:06:25ZCa2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes10.1038/s41598-017-04618-42045-2322https://doaj.org/article/112b8ebadb8d4885a17d2a0c00dfad042017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04618-4https://doaj.org/toc/2045-2322Abstract Opening of the mitochondrial permeability transition pore (mPTP) plays a major role in cell death during cardiac ischaemia-reperfusion. Adult isolated rodent cardiomyocytes are valuable cells to study the effect of drugs targeting mPTP. This study investigated whether the use of Ca2+ ionophores (A23187, ionomycin and ETH129) represent a reliable model to study inhibition of mPTP opening in cardiomyocytes. We monitored mPTP opening using the calcein/cobalt fluorescence technique in adult rat and wild type or cyclophilin D (CypD) knock-out mice cardiomyocytes. Cells were either treated with Ca2+ ionophores or subjected to hypoxia followed by reoxygenation. The ionophores induced mPTP-dependent swelling in isolated mitochondria. A23187, but not ionomycin, induced a decrease in calcein fluorescence. This loss could not be inhibited by CypD deletion and was explained by a direct interaction between A23187 and cobalt. ETH129 caused calcein loss, mitochondrial depolarization and cell death but CypD deletion did not alleviate these effects. In the hypoxia-reoxygenation model, CypD deletion delayed both mPTP opening and cell death occurring at the time of reoxygenation. Thus, Ca2+ ionophores are not suitable to induce CypD-dependent mPTP opening in adult murine cardiomyocytes. Hypoxia-reoxygenation conditions appear therefore as the most reliable model to investigate mPTP opening in these cells.Mathieu PanelBijan GhalehDidier MorinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mathieu Panel Bijan Ghaleh Didier Morin Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
description	Abstract Opening of the mitochondrial permeability transition pore (mPTP) plays a major role in cell death during cardiac ischaemia-reperfusion. Adult isolated rodent cardiomyocytes are valuable cells to study the effect of drugs targeting mPTP. This study investigated whether the use of Ca2+ ionophores (A23187, ionomycin and ETH129) represent a reliable model to study inhibition of mPTP opening in cardiomyocytes. We monitored mPTP opening using the calcein/cobalt fluorescence technique in adult rat and wild type or cyclophilin D (CypD) knock-out mice cardiomyocytes. Cells were either treated with Ca2+ ionophores or subjected to hypoxia followed by reoxygenation. The ionophores induced mPTP-dependent swelling in isolated mitochondria. A23187, but not ionomycin, induced a decrease in calcein fluorescence. This loss could not be inhibited by CypD deletion and was explained by a direct interaction between A23187 and cobalt. ETH129 caused calcein loss, mitochondrial depolarization and cell death but CypD deletion did not alleviate these effects. In the hypoxia-reoxygenation model, CypD deletion delayed both mPTP opening and cell death occurring at the time of reoxygenation. Thus, Ca2+ ionophores are not suitable to induce CypD-dependent mPTP opening in adult murine cardiomyocytes. Hypoxia-reoxygenation conditions appear therefore as the most reliable model to investigate mPTP opening in these cells.
format	article
author	Mathieu Panel Bijan Ghaleh Didier Morin
author_facet	Mathieu Panel Bijan Ghaleh Didier Morin
author_sort	Mathieu Panel
title	Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
title_short	Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
title_full	Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
title_fullStr	Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
title_full_unstemmed	Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes
title_sort	ca2+ ionophores are not suitable for inducing mptp opening in murine isolated adult cardiac myocytes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/112b8ebadb8d4885a17d2a0c00dfad04
work_keys_str_mv	AT mathieupanel ca2ionophoresarenotsuitableforinducingmptpopeninginmurineisolatedadultcardiacmyocytes AT bijanghaleh ca2ionophoresarenotsuitableforinducingmptpopeninginmurineisolatedadultcardiacmyocytes AT didiermorin ca2ionophoresarenotsuitableforinducingmptpopeninginmurineisolatedadultcardiacmyocytes
_version_	1718388431813345280

Ca2+ ionophores are not suitable for inducing mPTP opening in murine isolated adult cardiac myocytes

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