Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion

Koehler, Sybille and Brahler, Sebastian and Kuczkowski, Alexander and Binz, Julia and Hackl, Matthias J. and Hagmann, Henning and Hoehne, Martin and Vogt, Merly C. and Wunderlich, Claudia M. and Wunderlich, F. Thomas and Schweda, Frank and Schermer, Bernhard and Benzing, Thomas and Brinkkoetter, Paul T. (2016) Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion. SCIENTIFIC REPORTS, 6: 35400. ISSN 2045-2322,

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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.

Item Type: Article
Uncontrolled Keywords: FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; PROTEIN-COUPLED RECEPTORS; SLIT DIAPHRAGM; ACTIN CYTOSKELETON; CD2-ASSOCIATED PROTEIN; TRANSGENIC MICE; RENAL-FUNCTION; IN-VIVO; TRPC6;
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda
Depositing User: Dr. Gernot Deinzer
Date Deposited: 24 Apr 2019 11:27
Last Modified: 24 Apr 2019 11:27
URI: https://pred.uni-regensburg.de/id/eprint/4089

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