The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling
Abstract 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...
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| Format: | Article |
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Nature Portfolio
2017-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00406-2 |
| _version_ | 1818344331262558208 |
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| author | Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko |
| author_facet | Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko |
| author_sort | Daria V. Ilatovskaya |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T16:44:47Z |
| format | Article |
| id | doaj.art-be053c67314e45c0b972055d1c6a3177 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:44:47Z |
| publishDate | 2017-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-be053c67314e45c0b972055d1c6a31772022-12-21T23:38:12ZengNature PortfolioScientific Reports2045-23222017-03-017111210.1038/s41598-017-00406-2The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium HandlingDaria V. Ilatovskaya0Oleg Palygin1Vladislav Levchenko2Bradley T. Endres3Alexander Staruschenko4Department of Physiology, Medical College of WisconsinDepartment of Physiology, Medical College of WisconsinDepartment of Physiology, Medical College of WisconsinDepartment of Physiology, Medical College of WisconsinDepartment of Physiology, Medical College of WisconsinAbstract 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.https://doi.org/10.1038/s41598-017-00406-2 |
| spellingShingle | Daria V. Ilatovskaya Oleg Palygin Vladislav Levchenko Bradley T. Endres Alexander Staruschenko The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling Scientific Reports |
| title | The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling |
| title_full | The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling |
| title_fullStr | The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling |
| title_full_unstemmed | The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling |
| title_short | The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling |
| title_sort | role of angiotensin ii in glomerular volume dynamics and podocyte calcium handling |
| url | https://doi.org/10.1038/s41598-017-00406-2 |
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