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

Autoři: Viktor N. Tomilin aff001;  Mykola Mamenko aff002;  Oleg Zaika aff001;  Guohui Ren aff001;  Sean P. Marrelli aff003;  Lutz Birnbaumer aff004;  Oleh Pochynyuk aff001
Působiště autorů: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, United States of America aff001;  Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America aff002;  Department of Neurology, the University of Texas Health Science Center at Houston, Houston, Texas, United States of America aff003;  Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America aff004;  Institute of Biomedical Research (BIOMED), School of Medical Sciences, Catholic University of Argentina, Buenos Aires, Argentina aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


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.

Klíčová slova:

Cell membranes – Fluorescence imaging – Kidneys – Mannitol – Membrane trafficking – Permeability – Vasopressin – Hypotonic


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