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

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 os...

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Autores principales: Tomilin, Viktor N., Mamenko, Mykola, Zaika, Oleg, Ren, Guohui, Marrelli, Sean P., Birnbaumer, Lutz, Pochynyuk, Oleh
Formato: Artículo
Lenguaje:Inglés
Publicado: Public Library of Science 2020
Materias:
CALCIO
SEÑALIZACION INTRACELULAR
RIÑON
PRESION OSMOTICA
TRPC3
ACUAPORINAS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9867
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9867
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CALCIO
SEÑALIZACION INTRACELULAR
RIÑON
PRESION OSMOTICA
TRPC3
ACUAPORINAS
spellingShingle CALCIO
SEÑALIZACION INTRACELULAR
RIÑON
PRESION OSMOTICA
TRPC3
ACUAPORINAS
Tomilin, Viktor N.
Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
topic_facet CALCIO
SEÑALIZACION INTRACELULAR
RIÑON
PRESION OSMOTICA
TRPC3
ACUAPORINAS
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.
format Artículo
author Tomilin, Viktor N.
Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
author_facet Tomilin, Viktor N.
Mamenko, Mykola
Zaika, Oleg
Ren, Guohui
Marrelli, Sean P.
Birnbaumer, Lutz
Pochynyuk, Oleh
author_sort Tomilin, Viktor N.
title TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration
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
publisher Public Library of Science
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9867
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bdutipo_str Repositorios
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