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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Physiol
2016 ; 7
(ä): 351
Nephropedia Template TP
Front Physiol
2016[]; 7
(ä): 351
PMID27630573
show ga
The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE)
regulates renal function, including changes in glomerular function evoked during
tubuloglomerular feedback (TGF). This study describes the cellular actions of
20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured
podocytes combined with pharmacological and cell-biological manipulations of
cells. Bath superfusion of 20-HETE activates cationic currents that are blocked
by the pan-TRP blocker SKF-96365 and by 50 ?M La(3+), and which are attenuated
after siRNA knockdown of TRPC6 subunits. Similar currents are evoked by a
membrane-permeable analog of diacylgycerol (OAG), but OAG does not occlude
responses to maximally-activating concentrations of 20-HETE (20 ?M). Exposure to
20-HETE also increased steady-state surface abundance of TRPC6 subunits in
podocytes as assessed by cell-surface biotinylation assays, and increased
cytosolic concentrations of reactive oxygen species (ROS). TRPC6 activation by
20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable
superoxide dismutase mimic. Activation of TRPC6 by 20-HETE was also blocked when
whole-cell recording pipettes contained GDP-?S, indicating a role for either
small or heterotrimeric G proteins in the transduction cascade. Responses to
20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes
NADPH oxidase complexes with TRPC6 subunits in this cell type. In summary,
modulation of ionic channels in podocytes may contribute to glomerular actions of
20-HETE.