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• W4318573516 abstract "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. It was assumed that activation of TRPC6 channels leads directly to the Ca 2+ influx into cells. Another Ca 2+ influx pathway, a store-operated Ca 2+ entry (SOCE) via ORAI channels, was also shown to be disturbed during the diabetes development. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca 2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca 2+ imaging indicated the involvement of ORAI and sodium-calcium exchanger (NCX) in Ca 2+ entry induced upon store depletion. Ca 2+ inflow by NCX is a result of pronounced TRPC6-mediated Na + influx leading moreover to the membrane depolarization and ORAI suppression. In rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of SOCE in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca 2+ influx such that TRPC6 channels lost their sensitivity to Ca 2+ store depletion and ORAI-mediated Ca2+ entry is 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 in the pharmacological treatment of the early stages of diabetic nephropathy." @default.
• W4318573516 created "2023-01-31" @default.
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• W4318573516 date "2023-01-30" @default.
• W4318573516 modified "2023-09-27" @default.
• W4318573516 title "Reorganization and suppression of store-operated calcium entry in podocytes induced by diabetes type 2" @default.
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• W4318573516 doi "https://doi.org/10.21203/rs.3.rs-2511159/v1" @default.
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