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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 Am+J+Physiol+Renal+Physiol
2013 ; 304
(12
): F1428-37
Nephropedia Template TP
gab.com Text
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English Wikipedia
?ENaC is required for whole cell mechanically gated currents in renal vascular
smooth muscle cells
#MMPMID23552864
Chung WS
; Weissman JL
; Farley J
; Drummond HA
Am J Physiol Renal Physiol
2013[Jun]; 304
(12
): F1428-37
PMID23552864
show ga
Myogenic constrictor responses in small renal arteries and afferent arterioles
are suppressed in mice with reduced levels of ?-epithelial Na? channel
(?ENaC(m/m)). The underlying mechanism is unclear. Decreased activity of
voltage-gated calcium channels (VGCC) or mechanically gated ion channels and
increased activity of large conductance calcium-activated potassium (BK) channels
are a few possible mechanisms. The purpose of this study was to determine if
VGCC, BK, or mechanically gated ion channel activity was altered in renal
vascular smooth muscle cell (VSMC) from ?ENaC(m/m) mice. To address this, we used
whole cell patch-clamp electrophysiological approaches in freshly isolated renal
VSMCs. Compared with ?ENaC(+/+) controls, the current-voltage relationships for
VGCC and BK activity are similar in ?ENaC(m/m) mice. These findings suggest
neither VGCC nor BK channel dysfunction accounts for reduced myogenic
constriction in ?ENaC(m/m) mice. We then examined mechanically gated currents
using a novel in vitro assay where VSMCs are mechanically activated by stretching
an underlying elastomer. We found the mechanically gated currents, predominantly
carried by Na?, are observed with less frequency (87 vs. 43%) and have smaller
magnitude (-54.1 ± 12.5 vs. -20.9 ± 4.9 pA) in renal VSMCs from ?ENaC(m/m) mice.
Residual currents are expected in this model since VSMC ?ENaC expression is
reduced by 50%. These findings suggest ?ENaC is required for normal mechanically
gated currents in renal VSMCs and their disruption may account for the reduced
myogenic constriction in the ?ENaC(m/m) model. Our findings are consistent with
the role of ?ENaC as a VSMC mechanosensor and function of evolutionarily related
nematode degenerin proteins.