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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/120560
Ver los metadatos del registro completo
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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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1846782469678825472 |
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12.982451 |