The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice

Cai-Xia Lin,1,2 Jing-Li Gu,2 Ji-Min Cao11Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Physiology, Institute of Basic Medical Scienc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lin CX, Gu JL, Cao JM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	platinum nanoparticle transmembrane potential ion channel arrhythmia nanotoxicity heart Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f9f85e15f5a742f1b6a22dc30ec72b48
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f9f85e15f5a742f1b6a22dc30ec72b48
record_format	dspace
spelling	oai:doaj.org-article:f9f85e15f5a742f1b6a22dc30ec72b482021-12-02T06:38:50ZThe acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice1178-2013https://doaj.org/article/f9f85e15f5a742f1b6a22dc30ec72b482019-07-01T00:00:00Zhttps://www.dovepress.com/the-acute-toxic-effects-of-platinum-nanoparticles-on-ion-channels-tran-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cai-Xia Lin,1,2 Jing-Li Gu,2 Ji-Min Cao11Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of ChinaBackground: Platinum nanoparticles (PtNPs) have been considered a nontoxic nanomaterial and been clinically used in cancer chemotherapy. PtNPs can also be vehicle exhausts and environmental pollutants. These situations increase the possibility of human exposure to PtNPs. However, the potential biotoxicities of PtNPs including that on cardiac electrophysiology have been poorly understood.Methods: Ion channel currents of cardiomyocytes were recorded by patch clamp. Heart rhythm was monitored by electrocardiogram recording. Morphology and characteristics of PtNPs were examined by transmission electron microscopy, dynamic light scattering and electrophoretic light scattering analyses.Results: In cultured neonatal mice ventricular cardiomyocytes, PtNPs with diameters 5 nm (PtNP-5) and 70 nm (PtNP-70) concentration-dependently (10–9, – 10–5, g/mL) depolarized the resting potentials, suppressed the depolarization of action potentials and delayed the repolarization of action potentials. At the ion channel level, PtNPs decreased the current densities of INa, IK1 and Ito channels, but did not affect the channel activity kinetics. In vivo, PtNP-5 and PtNP-70 dose-dependently (3–10 mg/kg, i.v.) decreased the heart rate and induced complete atrioventricular conduction block (AVB) at higher doses. Both PtNP-5 and PtNP-70 (10–9, – 10–5, g/mL) did not significantly increase the generation of ROS and leak of lactate dehydrogenase (LDH) from cardiomyocytes within 5 mins after exposure except that only very high PtNP-5 (10–5, g/mL) slightly increased LDH leak. The internalization of PtNP-5 and PtNP-70 did not occur within 5 mins but occurred 1 hr after exposure.Conclusion: PtNP-5 and PtNP-70 have similar acute toxic effects on cardiac electrophysiology and can induce threatening cardiac conduction block. These acute electrophysiological toxicities of PtNPs are most likely caused by a nanoscale interference of PtNPs on ion channels at the extracellular side, rather than by oxidative damage or other slower biological processes.Keywords: platinum nanoparticle, transmembrane potential, ion channel, arrhythmia, nanotoxicity, heart  Lin CXGu JLCao JMDove Medical Pressarticleplatinum nanoparticletransmembrane potentialion channelarrhythmiananotoxicityheartMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5595-5609 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	platinum nanoparticle transmembrane potential ion channel arrhythmia nanotoxicity heart Medicine (General) R5-920
spellingShingle	platinum nanoparticle transmembrane potential ion channel arrhythmia nanotoxicity heart Medicine (General) R5-920 Lin CX Gu JL Cao JM The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
description	Cai-Xia Lin,1,2 Jing-Li Gu,2 Ji-Min Cao11Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of ChinaBackground: Platinum nanoparticles (PtNPs) have been considered a nontoxic nanomaterial and been clinically used in cancer chemotherapy. PtNPs can also be vehicle exhausts and environmental pollutants. These situations increase the possibility of human exposure to PtNPs. However, the potential biotoxicities of PtNPs including that on cardiac electrophysiology have been poorly understood.Methods: Ion channel currents of cardiomyocytes were recorded by patch clamp. Heart rhythm was monitored by electrocardiogram recording. Morphology and characteristics of PtNPs were examined by transmission electron microscopy, dynamic light scattering and electrophoretic light scattering analyses.Results: In cultured neonatal mice ventricular cardiomyocytes, PtNPs with diameters 5 nm (PtNP-5) and 70 nm (PtNP-70) concentration-dependently (10–9, – 10–5, g/mL) depolarized the resting potentials, suppressed the depolarization of action potentials and delayed the repolarization of action potentials. At the ion channel level, PtNPs decreased the current densities of INa, IK1 and Ito channels, but did not affect the channel activity kinetics. In vivo, PtNP-5 and PtNP-70 dose-dependently (3–10 mg/kg, i.v.) decreased the heart rate and induced complete atrioventricular conduction block (AVB) at higher doses. Both PtNP-5 and PtNP-70 (10–9, – 10–5, g/mL) did not significantly increase the generation of ROS and leak of lactate dehydrogenase (LDH) from cardiomyocytes within 5 mins after exposure except that only very high PtNP-5 (10–5, g/mL) slightly increased LDH leak. The internalization of PtNP-5 and PtNP-70 did not occur within 5 mins but occurred 1 hr after exposure.Conclusion: PtNP-5 and PtNP-70 have similar acute toxic effects on cardiac electrophysiology and can induce threatening cardiac conduction block. These acute electrophysiological toxicities of PtNPs are most likely caused by a nanoscale interference of PtNPs on ion channels at the extracellular side, rather than by oxidative damage or other slower biological processes.Keywords: platinum nanoparticle, transmembrane potential, ion channel, arrhythmia, nanotoxicity, heart
format	article
author	Lin CX Gu JL Cao JM
author_facet	Lin CX Gu JL Cao JM
author_sort	Lin CX
title	The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
title_short	The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
title_full	The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
title_fullStr	The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
title_full_unstemmed	The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
title_sort	acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/f9f85e15f5a742f1b6a22dc30ec72b48
work_keys_str_mv	AT lincx theacutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice AT gujl theacutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice AT caojm theacutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice AT lincx acutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice AT gujl acutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice AT caojm acutetoxiceffectsofplatinumnanoparticlesonionchannelstransmembranepotentialsofcardiomyocytesinvitroandheartrhythminvivoinmice
_version_	1718399850886725632

The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice

Ejemplares similares