The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling. Sci Rep 2017 Mar 22;7(1):299
Date
03/24/2017Pubmed ID
28331185Pubmed Central ID
PMC5428415DOI
10.1038/s41598-017-00406-2Scopus ID
2-s2.0-85026782870 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II-dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1-7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.
Author List
Ilatovskaya DV, Palygin O, Levchenko V, Endres BT, Staruschenko AMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Calcium
Imaging, Three-Dimensional
Kidney Glomerulus
Microscopy, Confocal
Patch-Clamp Techniques
Podocytes
Rats
TRPC6 Cation Channel
Vasoconstrictor Agents
