The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling

Abstract Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical...

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Autores principales:	Daria V. Ilatovskaya, Oleg Palygin, Vladislav Levchenko, Bradley T. Endres, Alexander Staruschenko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be053c67314e45c0b972055d1c6a3177
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spelling	oai:doaj.org-article:be053c67314e45c0b972055d1c6a31772021-12-02T15:05:40ZThe Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling10.1038/s41598-017-00406-22045-2322https://doaj.org/article/be053c67314e45c0b972055d1c6a31772017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00406-2https://doaj.org/toc/2045-2322Abstract Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II–dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1–7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.Daria V. IlatovskayaOleg PalyginVladislav LevchenkoBradley T. EndresAlexander StaruschenkoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
description	Abstract Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II–dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1–7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.
format	article
author	Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko
author_facet	Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko
author_sort	Daria V. Ilatovskaya
title	The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
title_short	The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
title_full	The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
title_fullStr	The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
title_full_unstemmed	The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
title_sort	role of angiotensin ii in glomerular volume dynamics and podocyte calcium handling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/be053c67314e45c0b972055d1c6a3177
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The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling

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