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标题：Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
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作者：Sybille Koehler ; Sebastian Brähler ; Alexander Kuczkowski 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep35400
语种：English
出版社：Springer Nature
摘要：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.