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dc.contributor.author
Tomilin, Viktor N.
dc.contributor.author
Mamenko, Mykola
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Zaika, Oleg
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Ren, Guohui
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Marrelli, Sean P.
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Birnbaumer, Lutz
dc.contributor.author
Pochynyuk, Oleh
dc.date.available
2020-12-16T13:06:21Z
dc.date.issued
2019-12
dc.identifier.citation
Tomilin, Viktor N.; Mamenko, Mykola; Zaika, Oleg; Ren, Guohui; Marrelli, Sean P.; et al.; TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration; Public Library of Science; Plos One; 14; 12; 12-2019
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/120560
dc.description.abstract
It is well-established that the kidney collecting duct (CD) plays a central role in regulation of systemic water homeostasis. Aquaporin 2 (AQP2)-dependent water reabsorption in the CD critically depends on the arginine vasopressin (AVP) antidiuretic input and the presence of a favorable osmotic gradient at the apical plasma membrane with tubular lumen being hypotonic compared to the cytosol. This osmotic difference creates a mechanical force leading to an increase in [Ca2+]i in CD cells. The significance of the osmosensitive [Ca2+]i signaling for renal water transport and urinary concentration remain unknown. To examine molecular mechanism and physiological relevance of osmosensitivity in the CD, we implemented simultaneous direct measurements of [Ca2+]i dynamics and the rate of cell swelling as a readout of the AQP2-dependent water reabsorption in freshly isolated split-opened CDs of wild type and genetically manipulated animals and combined this with immunofluorescent detection of AVP-induced AQP2 trafficking and assessment of systemic water balance. We identified the critical role of the Ca2+-permeable TRPC3 channel in osmosensitivity and water permeability in the CD. We further demonstrated that TRPC3 -/- mice exhibit impaired urinary concentration, larger urinary volume and a greater weight loss in response to water deprivation despite increased AVP levels and AQP2 abundance. TRPC3 deletion interfered with AQP2 translocation to the plasma membrane in response to water deprivation. In summary, we provide compelling multicomponent evidence in support of a critical contribution of TRPC3 in the CD for osmosensitivity and renal water handling.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
TRPC3
dc.subject.classification
Biología Celular, Microbiología
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-25T16:38:21Z
dc.journal.volume
14
dc.journal.number
12
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Tomilin, Viktor N.. University of Texas; Estados Unidos
dc.description.fil
Fil: Mamenko, Mykola. Augusta University; Estados Unidos
dc.description.fil
Fil: Zaika, Oleg. University of Texas; Estados Unidos
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Fil: Ren, Guohui. University of Texas; Estados Unidos
dc.description.fil
Fil: Marrelli, Sean P.. University of Texas; Estados Unidos
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Pochynyuk, Oleh. University of Texas; Estados Unidos
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0226381
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226381
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