Cargando…

Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion

Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusivel...

Descripción completa

Detalles Bibliográficos
Autores principales: Koehler, Sybille, Brähler, Sebastian, Kuczkowski, Alexander, Binz, Julia, Hackl, Matthias J., Hagmann, Henning, Höhne, Martin, Vogt, Merly C., Wunderlich, Claudia M., Wunderlich, F. Thomas, Schweda, Frank, Schermer, Bernhard, Benzing, Thomas, Brinkkoetter, Paul T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069688/
https://www.ncbi.nlm.nih.gov/pubmed/27759104
http://dx.doi.org/10.1038/srep35400
_version_ 1782460987442462720
author Koehler, Sybille
Brähler, Sebastian
Kuczkowski, Alexander
Binz, Julia
Hackl, Matthias J.
Hagmann, Henning
Höhne, Martin
Vogt, Merly C.
Wunderlich, Claudia M.
Wunderlich, F. Thomas
Schweda, Frank
Schermer, Bernhard
Benzing, Thomas
Brinkkoetter, Paul T.
author_facet Koehler, Sybille
Brähler, Sebastian
Kuczkowski, Alexander
Binz, Julia
Hackl, Matthias J.
Hagmann, Henning
Höhne, Martin
Vogt, Merly C.
Wunderlich, Claudia M.
Wunderlich, F. Thomas
Schweda, Frank
Schermer, Bernhard
Benzing, Thomas
Brinkkoetter, Paul T.
author_sort Koehler, Sybille
collection PubMed
description Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals. Activation of the engineered G-protein coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca(2+) peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca(2+) peak did neither affect glomerular perfusion nor filtration in the animals. Moreover, no obvious alterations in the glomerular morphology could be observed. Taken together, these in vivo findings suggest that chronic alterations and calcium overload rather than an induction of transient Ca(2+) peaks contribute to podocyte disease.
format Online
Article
Text
id pubmed-5069688
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-50696882016-10-26 Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion Koehler, Sybille Brähler, Sebastian Kuczkowski, Alexander Binz, Julia Hackl, Matthias J. Hagmann, Henning Höhne, Martin Vogt, Merly C. Wunderlich, Claudia M. Wunderlich, F. Thomas Schweda, Frank Schermer, Bernhard Benzing, Thomas Brinkkoetter, Paul T. Sci Rep Article Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals. Activation of the engineered G-protein coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca(2+) peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca(2+) peak did neither affect glomerular perfusion nor filtration in the animals. Moreover, no obvious alterations in the glomerular morphology could be observed. Taken together, these in vivo findings suggest that chronic alterations and calcium overload rather than an induction of transient Ca(2+) peaks contribute to podocyte disease. Nature Publishing Group 2016-10-19 /pmc/articles/PMC5069688/ /pubmed/27759104 http://dx.doi.org/10.1038/srep35400 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Koehler, Sybille
Brähler, Sebastian
Kuczkowski, Alexander
Binz, Julia
Hackl, Matthias J.
Hagmann, Henning
Höhne, Martin
Vogt, Merly C.
Wunderlich, Claudia M.
Wunderlich, F. Thomas
Schweda, Frank
Schermer, Bernhard
Benzing, Thomas
Brinkkoetter, Paul T.
Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title_full Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title_fullStr Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title_full_unstemmed Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title_short Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
title_sort single and transient ca(2+) peaks in podocytes do not induce changes in glomerular filtration and perfusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069688/
https://www.ncbi.nlm.nih.gov/pubmed/27759104
http://dx.doi.org/10.1038/srep35400
work_keys_str_mv AT koehlersybille singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT brahlersebastian singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT kuczkowskialexander singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT binzjulia singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT hacklmatthiasj singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT hagmannhenning singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT hohnemartin singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT vogtmerlyc singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT wunderlichclaudiam singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT wunderlichfthomas singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT schwedafrank singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT schermerbernhard singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT benzingthomas singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion
AT brinkkoetterpault singleandtransientca2peaksinpodocytesdonotinducechangesinglomerularfiltrationandperfusion