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TRPC3 Facilitates Adaptation of Collecting Duct Cells to Changes in Osmolality
Author(s) -
Mamenko Mykola,
Zaika Oleg,
Boukelmoune Nabila,
O'Neil Roger,
Pochynyuk Oleh
Publication year - 2015
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.29.1_supplement.666.17
Subject(s) - trpc3 , extracellular , tonicity , chemistry , plasma osmolality , biophysics , osmoregulation , osmotic shock , microbiology and biotechnology , osmotic concentration , medicine , endocrinology , biology , biochemistry , transient receptor potential channel , sodium , receptor , trpc , ecology , organic chemistry , salinity , gene
Mechanical stress induced by changes in tubular flow rate and osmotic gradients is viewed to be an important regulator of the water and electrolytes transport in the collecting duct (CD). Our recent experimental effort identified that pharmacological inhibition or genetic ablation of TRPV4 precluded [Ca 2+ ] i responses to elevated flow but not to hypotonicity suggesting involvement of discrete signaling determinants. Here we combined direct measurements of [Ca 2+ ] i dynamics in freshly isolated split‐opened CDs with genetic tools to unravel molecular components of cellular responses to decreased osmolality. [Ca 2+ ] i elevations elicited by hypotonicity in CD cells were abolished upon removal of extracellular Ca 2+ , but not by depletion of the endoplasmic reticulum stores, indicating a critical role of direct Ca 2+ entry via the plasma membrane. Inhibition of Ca 2+ ‐permeable TRPC3 channel markedly diminishes the amplitude of [Ca 2+ ] i signal induced by hypotonic stimuli in the CD. Interestingly, genetic deletion of TRPC3 significantly increases the activation threshold for [Ca 2+ ] i responses to changes in extracellular osmolality. Water deprivation (18 hours) greatly augmented sensitivity of CD cells to extracellular osmolality in wild‐type, but only mildly in TRPC3‐/‐ mice. At the systemic level, TRPC3 ablation results in a transient defect in urinary concentration ability in response to water deprivation. Overall, our findings demonstrate that elevated flow and osmotic gradients recruit distinct signaling cascades to increase [Ca 2+ ] i in CD cells. Genetic ablation of TRPC3 disturbs sensitivity of CD cells to hypotonic stress contributing to delayed adaptation of the kidney to restricted water intake.