Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
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Single and Transient Ca2+ 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.
In: SCI REP-UK, Vol. 6, 19.10.2016, p. 35400.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
AU - Koehler, Sybille
AU - Brähler, Sebastian
AU - Kuczkowski, Alexander
AU - Binz, Julia
AU - Hackl, Matthias J
AU - Hagmann, Henning
AU - Höhne, Martin
AU - Vogt, Merly C
AU - Wunderlich, Claudia M
AU - Wunderlich, F Thomas
AU - Schweda, Frank
AU - Schermer, Bernhard
AU - Benzing, Thomas
AU - Brinkkoetter, Paul T
PY - 2016/10/19
Y1 - 2016/10/19
N2 - 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.
AB - 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.
U2 - 10.1038/srep35400
DO - 10.1038/srep35400
M3 - SCORING: Journal article
C2 - 27759104
VL - 6
SP - 35400
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -