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Article: Functional distinctions in cytosolic calcium regulation between cells of the glomerular filtration barrier

TitleFunctional distinctions in cytosolic calcium regulation between cells of the glomerular filtration barrier
Authors
KeywordsCalcium
Flufenamic acid
Glomerular endothelial cells
Podocytes
TRPC6
Issue Date2010
Citation
Cell Calcium, 2010, v. 48 n. 1, p. 44-53 How to Cite?
AbstractThe importance of intracellular calcium ([Ca2+]i) regulation in the glomerular filtration barrier (GFB) has recently been highlighted by mutations in the cation channel TRPC6, resulting in a renal-specific phenotype. We examined the effects of FFA, a tool that can activate TRPC6, on [Ca2+]i in human conditionally immortalised glomerular endothelial cells (ciGEnC) and human podocytes (ciPod) that form the GFB. Changes in [Ca2+]i stimulated by FFA were measured in Fura 2-AM loaded cells. In GEnC, cell activation by FFA was dependent on external Ca2+, yet in ciPod it was not. Depletion of internal Ca2+ stores with thapsigargin did not affect cell activation by FFA in ciGEnC, but inhibited it in ciPod in a nephrin-dependent manner, demonstrated using nephrin deficient (ND) ciPod in conjunction with nephrin rescue experiments. FFA induced [Ca2+]i store release in ciPod, but not in ciGEnC or ND ciPod. In parallel, there were differences in the localisation of overexpressed TRPC6 between ciGEnC and ciPod. Furthermore, co-transfection of nephrin with TRPC6 in HEK293 cells reduced the FFA-induced increase in [Ca2+]i and nephrin clustering altered TRPC6 distribution. In conclusion, cell activation by FFA in podocytes stimulates the opening of a Ca2+ channel, probably TRPC6, in a nephrin-dependent manner with a different activation profile to GEnC. © 2010 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/195488
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 1.309
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFoster, RR-
dc.contributor.authorWelsh, GI-
dc.contributor.authorSatchell, SC-
dc.contributor.authorMarlow, RD-
dc.contributor.authorWherlock, MD-
dc.contributor.authorPons, D-
dc.contributor.authorMathieson, PW-
dc.contributor.authorBates, DO-
dc.contributor.authorSaleem, MA-
dc.date.accessioned2014-02-28T06:12:13Z-
dc.date.available2014-02-28T06:12:13Z-
dc.date.issued2010-
dc.identifier.citationCell Calcium, 2010, v. 48 n. 1, p. 44-53-
dc.identifier.issn0143-4160-
dc.identifier.urihttp://hdl.handle.net/10722/195488-
dc.description.abstractThe importance of intracellular calcium ([Ca2+]i) regulation in the glomerular filtration barrier (GFB) has recently been highlighted by mutations in the cation channel TRPC6, resulting in a renal-specific phenotype. We examined the effects of FFA, a tool that can activate TRPC6, on [Ca2+]i in human conditionally immortalised glomerular endothelial cells (ciGEnC) and human podocytes (ciPod) that form the GFB. Changes in [Ca2+]i stimulated by FFA were measured in Fura 2-AM loaded cells. In GEnC, cell activation by FFA was dependent on external Ca2+, yet in ciPod it was not. Depletion of internal Ca2+ stores with thapsigargin did not affect cell activation by FFA in ciGEnC, but inhibited it in ciPod in a nephrin-dependent manner, demonstrated using nephrin deficient (ND) ciPod in conjunction with nephrin rescue experiments. FFA induced [Ca2+]i store release in ciPod, but not in ciGEnC or ND ciPod. In parallel, there were differences in the localisation of overexpressed TRPC6 between ciGEnC and ciPod. Furthermore, co-transfection of nephrin with TRPC6 in HEK293 cells reduced the FFA-induced increase in [Ca2+]i and nephrin clustering altered TRPC6 distribution. In conclusion, cell activation by FFA in podocytes stimulates the opening of a Ca2+ channel, probably TRPC6, in a nephrin-dependent manner with a different activation profile to GEnC. © 2010 Elsevier Ltd.-
dc.languageeng-
dc.relation.ispartofCell Calcium-
dc.subjectCalcium-
dc.subjectFlufenamic acid-
dc.subjectGlomerular endothelial cells-
dc.subjectPodocytes-
dc.subjectTRPC6-
dc.titleFunctional distinctions in cytosolic calcium regulation between cells of the glomerular filtration barrier-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ceca.2010.06.005-
dc.identifier.pmid20674014-
dc.identifier.scopuseid_2-s2.0-77956010985-
dc.identifier.volume48-
dc.identifier.issue1-
dc.identifier.spage44-
dc.identifier.epage53-
dc.identifier.isiWOS:000282137200006-
dc.identifier.issnl0143-4160-

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