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TRPC3 serves as a link between osmosensitivity and water transport in the mouse collecting duct
Author(s) -
Tomilin Viktor,
Mamenko Mykola,
Zaika Oleg,
Pochynyuk Oleh M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.970.2
Subject(s) - trpc3 , reabsorption , duct (anatomy) , extracellular , osmotic concentration , aquaporin , stimulation , intracellular , microbiology and biotechnology , water transport , chemistry , renal sodium reabsorption , medicine , biology , endocrinology , kidney , anatomy , biochemistry , transient receptor potential channel , trpc , water flow , receptor , engineering , environmental engineering
Collecting duct serves as the primary site of controlled water reabsorption driven by osmotic gradient in the kidney. Cells of the collecting duct sense the changes of the extracellular osmolarity and react by elevating intracellular calcium via a yet unidentified mechanism. Moreover, the relation between osmosensitivity and water transport is poorly understood. Ca2+ permeable TRPC3 channel has been proposed to participate in mechanosensitive responses in different cell types. Previous evidence demonstrates prominent expression of this channel in the collecting duct cells. Using ratiometric Fura 2‐based [Ca2+]i imaging in freshly isolated split‐opened mouse collecting ducts, we found that pharmacological inhibition of TRPC3 with Pyr3 significantly reduces cellular responses to hypotonicity. Consistently, genetic TRPC3 deletion markedly impairs sensitivity of the collecting duct cells to decreases in extracellular osmolarity. Furthermore, collecting duct cells of TRPC3 −/− mice fail to properly regulate their volume in response to acute hypotonic challenge. Stimulation of water reabsorption with water deprivation exacerbates differences in collecting duct osmosensitivity between wild type and TRPC3 −/− mice and also transiently reduces urinary concentration ability in the mutant animals. We conclude that TRPC3‐mediated Ca2+ influx during hypotonicity is important for proper stimulation of water reabsorption in the collecting duct. Support or Funding Information Supported by AHA and NIH grants