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TRPV4 channel activation is required for flow‐dependent K + secretion/BK channel activation in mouse cortical collecting duct (CCD)
Author(s) -
Jin Min,
Pochynyuk Oleh,
O'Neil Roger G.
Publication year - 2011
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.25.1_supplement.1041.29
Subject(s) - trpv4 , bk channel , chemistry , biophysics , ruthenium red , iberiotoxin , secretion , patch clamp , depolarization , microbiology and biotechnology , membrane potential , transient receptor potential channel , potassium channel , biology , biochemistry , calcium , receptor , organic chemistry
Flow‐dependent K + secretion by the late distal tubule (CNT and CCD) can lead to inappropriate K + loss via activation of Ca 2+ ‐dependent BK channels. We have previously shown that TRPV4 is a flow‐dependent Ca 2+ ‐permeable channel. In the current study, immunohistochemical labeling of mouse kidney sections demonstrated that TRPV4 and BKα co‐localize in CCD with strong expression in aquaporin‐2 positive principal cells (PC) and weak expression in intercalated cells (IC). Separately, cytosolic Ca 2+ levels, [Ca 2+ ]i, were monitored (fura 2 fluorescence) in isolated, split‐open CCDs. Fluid flow over the luminal surface induced a sustained increase in [Ca 2+ ]i in both PC and IC (peanut agglutinin‐binding cells) which was abolished by addition of ruthenium red (3 μM), a TRPV channel inhibitor. In flow‐activated cells, addition of iberiotoxin (25 nM), a BK channel inhibitor, induced a rapid fall in the flow‐induced [Ca 2+ ]i in both PCs and ICs, reflecting membrane depolarization with BK inhibition. The flow‐induced activation was abolished in CCD from TRPV4 −/− knockout mice. It is concluded that TRPV4 and BK are expressed in both PC and IC and that flow activates TRPV4 leading to Ca 2+ influx and activation of BK (and K + secretion) in both cell types. Differential expression of channels may lead to divergent flow‐dependent K + secretion between PC and IC. Supported by NIH grant DK070950 (RGO) and AHA SDG2230391 (OP).