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Expression and function of the Ca2+‐dependent SK3 K+ channel in mouse cortical collecting duct: Regulation by TRPV4
Author(s) -
Berrout Jonathan,
Mamenko Mykola,
Zaika Oleg L,
Pochynyuk Oleh,
O'Neil Roger G
Publication year - 2013
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.27.1_supplement.912.14
Subject(s) - bk channel , trpv4 , chemistry , sk channel , secretion , microbiology and biotechnology , biophysics , membrane potential , medicine , endocrinology , ion channel , biology , receptor , biochemistry
The cortical collecting duct (CCD) is a major site of flow‐induced K + secretion that is thought to be predominantly mediated by the large conductance Ca 2+ ‐dependent K + channel (BK). We now report the expression of the small conductance, Ca 2+ ‐dependent, SK3 K + channel in mouse CCD. Expression of SK3 in fixed kidney sections was detected by immunohistochemistry in both principal cells (PC, Aquaporin 2‐positive cells) and intercalated cells (IC) with dominant staining at the luminal cell border (modest staining at basolateral border). Membrane potential measurements demonstrated that activation of TRPV4, using the selective TRPV4‐agonist (GSK1016790A), induced calcium influx and activation of SK3 (and BK) in isolated, split‐open CCD. High flow rates (a 10‐fold increase in flow) induced calcium influx and revealed activation of both SK3 and BK channels in CCD, effects that were abolished by application of the selective TRPV4‐ antagonist (HC‐067047). We conclude that SK3 is expressed in both PC and IC cells of the CCD, and that TRPV4 mediates activation of SK3 and BK. Further, these findings suggest that SK3 channels may play an important role, alongside BK channels, in mediating K + secretion under conditions of high luminal flow rate.