TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration

Autores
Tomilin, Viktor N.; Mamenko, Mykola; Zaika, Oleg; Ren, Guohui; Marrelli, Sean P.; Birnbaumer, Lutz; Pochynyuk, Oleh
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Tomilin, Viktor N.. University of Texas; Estados Unidos
Fil: Mamenko, Mykola. Augusta University; Estados Unidos
Fil: Zaika, Oleg. University of Texas; Estados Unidos
Fil: Ren, Guohui. University of Texas; Estados Unidos
Fil: Marrelli, Sean P.. University of Texas; Estados Unidos
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
Fil: Pochynyuk, Oleh. University of Texas; Estados Unidos
Materia
TRPC3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120560

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spelling TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentrationTomilin, Viktor N.Mamenko, MykolaZaika, OlegRen, GuohuiMarrelli, Sean P.Birnbaumer, LutzPochynyuk, OlehTRPC3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It 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.Fil: Tomilin, Viktor N.. University of Texas; Estados UnidosFil: Mamenko, Mykola. Augusta University; Estados UnidosFil: Zaika, Oleg. University of Texas; Estados UnidosFil: Ren, Guohui. University of Texas; Estados UnidosFil: Marrelli, Sean P.. University of Texas; Estados UnidosFil: 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; ArgentinaFil: Pochynyuk, Oleh. University of Texas; Estados UnidosPublic Library of Science2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120560Tomilin, 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; 12-20191932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0226381info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226381info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:09:16Zoai:ri.conicet.gov.ar:11336/120560instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:09:17.255CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
title TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
spellingShingle TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
Tomilin, Viktor N.
TRPC3
title_short TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
title_full TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
title_fullStr TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
title_full_unstemmed TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
title_sort TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
dc.creator.none.fl_str_mv Tomilin, Viktor N.
Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
author Tomilin, Viktor N.
author_facet Tomilin, Viktor N.
Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
author_role author
author2 Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC3
topic TRPC3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Tomilin, Viktor N.. University of Texas; Estados Unidos
Fil: Mamenko, Mykola. Augusta University; Estados Unidos
Fil: Zaika, Oleg. University of Texas; Estados Unidos
Fil: Ren, Guohui. University of Texas; Estados Unidos
Fil: Marrelli, Sean P.. University of Texas; Estados Unidos
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
Fil: Pochynyuk, Oleh. University of Texas; Estados Unidos
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120560
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
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120560
identifier_str_mv 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
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0226381
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226381
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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