Inhibition of the TRPC5 ion channel protects the kidney filter

Thomas Schaldecker, Sookyung Kim, Constantine Tarabanis, Dequan Tian, Samy Hakroush, Philip Castonguay, Wooin Ahn, Hanna Wallentin, Hans Heid, Corey R. Hopkins, Craig W. Lindsley, Antonio Riccio, Lisa Buvall, Astrid Weins, Anna Greka

Research output: Contribution to journalArticle

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Abstract

An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca 2+-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease.

Original languageEnglish (US)
Pages (from-to)5298-5309
Number of pages12
JournalJournal of Clinical Investigation
Volume123
Issue number12
DOIs
StatePublished - Dec 2 2013

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Podocytes
Albuminuria
Ion Channels
rac1 GTP-Binding Protein
Kidney Glomerulus
Kidney
Kidney Diseases
Renal Insufficiency
Actins
Blood Proteins
Albumins
Cardiovascular Diseases
Urine
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schaldecker, T., Kim, S., Tarabanis, C., Tian, D., Hakroush, S., Castonguay, P., ... Greka, A. (2013). Inhibition of the TRPC5 ion channel protects the kidney filter. Journal of Clinical Investigation, 123(12), 5298-5309. https://doi.org/10.1172/JCI71165

Inhibition of the TRPC5 ion channel protects the kidney filter. / Schaldecker, Thomas; Kim, Sookyung; Tarabanis, Constantine; Tian, Dequan; Hakroush, Samy; Castonguay, Philip; Ahn, Wooin; Wallentin, Hanna; Heid, Hans; Hopkins, Corey R.; Lindsley, Craig W.; Riccio, Antonio; Buvall, Lisa; Weins, Astrid; Greka, Anna.

In: Journal of Clinical Investigation, Vol. 123, No. 12, 02.12.2013, p. 5298-5309.

Research output: Contribution to journalArticle

Schaldecker, T, Kim, S, Tarabanis, C, Tian, D, Hakroush, S, Castonguay, P, Ahn, W, Wallentin, H, Heid, H, Hopkins, CR, Lindsley, CW, Riccio, A, Buvall, L, Weins, A & Greka, A 2013, 'Inhibition of the TRPC5 ion channel protects the kidney filter', Journal of Clinical Investigation, vol. 123, no. 12, pp. 5298-5309. https://doi.org/10.1172/JCI71165
Schaldecker T, Kim S, Tarabanis C, Tian D, Hakroush S, Castonguay P et al. Inhibition of the TRPC5 ion channel protects the kidney filter. Journal of Clinical Investigation. 2013 Dec 2;123(12):5298-5309. https://doi.org/10.1172/JCI71165
Schaldecker, Thomas ; Kim, Sookyung ; Tarabanis, Constantine ; Tian, Dequan ; Hakroush, Samy ; Castonguay, Philip ; Ahn, Wooin ; Wallentin, Hanna ; Heid, Hans ; Hopkins, Corey R. ; Lindsley, Craig W. ; Riccio, Antonio ; Buvall, Lisa ; Weins, Astrid ; Greka, Anna. / Inhibition of the TRPC5 ion channel protects the kidney filter. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 12. pp. 5298-5309.
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