title: Single and Transient Ca2+Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion.
abstract: Chronic alterations in calcium (Ca2+) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca2+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 Ca2+levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca2+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 Ca2+peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca2+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 Ca2+peaks contribute to podocyte disease.
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Sybille
authors.initials: S
authors.lastname: Koehler
authors.affiliation: Department of Pathology &Immunology, Division of Immunobiology, Washington University School of Medicine, St Louis, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brähler
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kuczkowski
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Binz
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Hackl
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Hagmann
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Höhne
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Department of Biological Sciences, Columbia University, New York, NY, USA.
authors.forename: Merly C
authors.initials: MC
authors.lastname: Vogt
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Wunderlich
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: F Thomas
authors.initials: FT
authors.lastname: Wunderlich
authors.affiliation: Department of Physiology, University of Regensburg, Regensburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Brinkkoetter