Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats

Author:

Gusev Konstantin1,Shalygin Alexey1,Kolesnikov Dmitrii1,Shuyskiy Leonid1,Makeenok Sofia1,Glushankova Lyubov1,Sivak Konstantin2ORCID,Yakovlev Kirill2ORCID,Orshanskaya Yana2,Wang Guanghui3,Bakhtyukov Andrey4ORCID,Derkach Kira4ORCID,Shpakov Alexander4ORCID,Kaznacheyeva Elena1ORCID

Affiliation:

1. Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia

2. Smorodintsev Research Institute of Influenza WHO National Influenza Centre of Russia, St. Petersburg 197376, Russia

3. Department of Pharmacology, College of Pharmaceutic Sciences, Soochow University, Suzhou 215031, China

4. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia

Abstract

Type 2 diabetes mellitus (DM2) is a widespread metabolic disorder that results in podocyte damage and diabetic nephropathy. Previous studies demonstrated that TRPC6 channels play a pivotal role in podocyte function and their dysregulation is associated with development of different kidney diseases including nephropathy. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca2+ imaging indicated the involvement of ORAI and sodium–calcium exchanger in Ca2+ entry induced upon store depletion. In male rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of a store-operated Ca2+ entry (SOCE) in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca2+ influx such that TRPC6 channels lost their sensitivity to Ca2+ store depletion and ORAI-mediated Ca2+ entry was suppressed in TRPC6-independent manner. Altogether our data provide new insights into the mechanism of SOCE organization in podocytes in the norm and in pathology, which should be taken into account when developing pharmacological treatment of the early stages of diabetic nephropathy.

Funder

Russian Scientific Foundation

National Natural Science Foundation of China

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. STIM Proteins: The Gas and Brake of Calcium Entry in Neurons;Neuroscience Bulletin;2024-09-12

2. Non-voltage-gated Ca2+ channel signaling in glomerular cells in kidney health and disease;American Journal of Physiology-Renal Physiology;2024-08-01

3. Role of Podocyte in Kidney Disease;Frontiers in Bioscience-Landmark;2024-07-11

4. Calcium signalling and transport in the kidney;Nature Reviews Nephrology;2024-04-19

5. TRP channels in renal disease. Lessons from Polycystin-2 (TRPP2);TRP Channels as Therapeutic Targets;2024

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