title: Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
abstract: A key role for podocytes in the pathogenesis of proteinuric renal diseases has been established. Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux. Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis. Here we examined the effects of angiotensin II on intracellular calcium ion levels and endogenous channels in intact podocytes of freshly isolated decapsulated mouse glomeruli. An ion channel with distinct TRPC6 properties was identified in wild-type, but was absent in TRPC6 knockout mice. Single-channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability. Angiotensin II evoked intracellular calcium transients in the wild-type podocytes, which was blunted in TRPC6 knockout glomeruli. Pan-TRPC inhibitors gadolinium and SKF 96365 reduced the response in wild-type glomerular epithelial cells, whereas the transient in TRPC6 knockout animals was not affected. Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
authors.affiliation: 1] Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA [2] Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Ilatovskaya
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Chubinskiy-Nadezhdin
authors.affiliation: 1] Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation [2] Department of Medical Physics, St. Petersburg State Polytechnical University, St. Petersburg, Russian Federation.
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Negulyaev
authors.affiliation: Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Transmembrane Signaling Group, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003412:Cricetulus; D005682:Gadolinium / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D000804:Angiotensin II; D005682:Gadolinium; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium