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Angiotensin II Dependent Regulation of TRPC6 Calcium Channels in the Podocytes of the STZ‐induced Type 1 Diabetic Dahl SS Rats
Author(s) -
Ilatovskaya Daria,
Palygin Oleg,
Lowing Andrea,
Levchenko Vladislav,
Staruschenko Alexander
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.964.1
Subject(s) - nephrin , trpc6 , endocrinology , medicine , podocyte , diabetic nephropathy , glomerulosclerosis , angiotensin ii , chemistry , l type calcium channel , diabetes mellitus , kidney , proteinuria , calcium , voltage dependent calcium channel , transient receptor potential channel , receptor
Injury to podocytes (terminally differentiated epithelial cells of the glomeruli) is considered a major contributor to diabetic kidney disease, when podocyte loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling in these cells, f.i. due to abnormal activation of the TRPC channels stimulated by Angiotensin II (Ang II). The goal of this study was to assess the ramifications of type 1 diabetes on Ang II mediated calcium influx in the podocytes. Diabetes was induced in the 6 week old Dahl salt‐sensitive rats by an injection of STZ, which resulted in weight loss, excessive urination and renal damage typical for diabetic nephropathy. During next 12 weeks rats were monitored to ensure hyperglycemia; biochemical analyses showed progressive proteinuria and high nephrin excretion, whereas excretion of Na + and K + remained normal. Patch‐clamp electrophysiology performed on podocytes of the isolated glomeruli showed increased basal TRPC6 channel activity (FNP o ) in the STZ‐treated animals compared to controls (41% and 18% of patches, respectively), and a 5‐fold elevation of the channels open probability in response to 10 µM Ang II (the conductance (18 pS) and reversal potential of the channel (0 mV) remained unchanged). Ratiometric confocal measurements in glomeruli loaded with Fluo4/FuraRed dyes showed increased calcium influx in response to Ang II in diabetic rats compared to control animals. We can conclude from these data that Ang II‐dependent TRPC6 channels regulation plays a critical role in the glomerular filtration barrier destruction during type 1 diabetes.