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TRPV4 is a mechanotransducer of fluid flow in principal cells (PC) and intercalated cells (IC) of the renal collecting duct system
Author(s) -
Berrout Jonathan,
Jin Min,
Mamenko Mykola,
Zaika Oleg L,
Pochynyuk Oleh,
O'Neil Roger G
Publication year - 2012
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.26.1_supplement.867.26
Subject(s) - trpv4 , chemistry , ruthenium red , microbiology and biotechnology , duct (anatomy) , colocalization , transient receptor potential channel , biophysics , anatomy , biology , receptor , biochemistry , organic chemistry , calcium
The sites of expression and function of TRPV4, a Ca2+‐permeable channel, were evaluated in the mouse kidney. Immunhistochemical localization studies in kidney slices and isolated split‐opened connecting tubule (CNT) and cortical collecting duct (CCD) demonstrated strong expression of TRPV4 along the entire collecting duct system with no detectable expression in upstream segments. Expression was highest in PC, the aquaporin‐2 (AQP‐2) positive cells, with a high level of colocalization with AQP‐2 near the apical/subapical region, and low in IC (AQP‐2 negative). Separate Ca2+ imaging studies (fura 2 imaging) of split‐opened CNT/CDD on coverslips, demonstrate that GSK1016790A (50 nM), a selective TRPV4 agonist, activates TRPV4 channels in both PC and IC, although less robustly in IC. Further, a step increase in fluid flow over the luminal surface rapidly stimulated a sustained Ca2+ influx in PC and IC of both CNT and CCD. This response was abolished following treatment with ruthenium red, a TRPV channel blocker, or in CNT/CCD isolated from TRPV4 knockout animals. Inhibition of the phospholipase C (PLC) signaling cascade with the PLC inhibitor, U73122 (10 uM), largely abolished the flow‐dependent response, implicating TRPV4 as a downstream transducer of flow. It is concluded that TRPV4 is widely expressed in the collecting duct system and that it functions as a mechanotransducer of fluid flow in both PC and IC.