PMID- 22933298
OWN - NLM
STAT- MEDLINE
DCOM- 20130124
LR  - 20141120
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 303
IP  - 9
DP  - 2012 Nov 1
TI  - Aldosterone-dependent and -independent regulation of the epithelial sodium 
      channel (ENaC) in mouse distal nephron.
PG  - F1289-99
LID - 10.1152/ajprenal.00247.2012 [doi]
AB  - Aldosterone is thought to be the main hormone to stimulate the epithelial sodium 
      channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the 
      late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire 
      collecting duct (CD). There is immunohistochemical evidence for an axial gradient 
      of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. 
      However, most of our knowledge about renal ENaC function stems from studies in 
      the cortical collecting duct (CCD). Here we investigated ENaC function in the 
      transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on 
      different sodium diets to vary plasma aldosterone levels. Single-channel 
      recordings demonstrated amiloride-sensitive Na(+) channels in DCT2/CNT with 
      biophysical properties typical for ENaC previously described in CNT/CCD. In 
      animals maintained on a standard salt diet, the average ENaC-mediated whole cell 
      current (DeltaI(ami)) was higher in DCT2/CNT than in CNT/CCD. A low salt diet 
      increased DeltaI(ami) in CNT/CCD but had little effect on DeltaI(ami) in DCT2/CNT. To 
      investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, 
      we used aldosterone synthase knockout (AS(-/-)) mice that lack aldosterone. In 
      CNT/CCD of AS(-/-) mice, DeltaI(ami) was lower than that in wild-type (WT) animals 
      and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS(-/-) 
      mice, DeltaI(ami) was similar to that in DCT2/CNT of WT animals both on a standard 
      and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely 
      independent of aldosterone which is in contrast to its known aldosterone 
      sensitivity in CNT/CCD.
FAU - Nesterov, Viatcheslav
AU  - Nesterov V
AD  - Institut fur Zellulare und Molekulare Physiologie, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Germany.
FAU - Dahlmann, Anke
AU  - Dahlmann A
FAU - Krueger, Bettina
AU  - Krueger B
FAU - Bertog, Marko
AU  - Bertog M
FAU - Loffing, Johannes
AU  - Loffing J
FAU - Korbmacher, Christoph
AU  - Korbmacher C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120829
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Sodium, Dietary)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 1.14.15.4 (Cytochrome P-450 CYP11B2)
SB  - IM
CIN - Am J Physiol Renal Physiol. 2012 Nov 1;303(9):F1287-8. PMID: 22993072
MH  - Aldosterone/*physiology
MH  - Animals
MH  - Cytochrome P-450 CYP11B2/deficiency/genetics/physiology
MH  - Epithelial Sodium Channels/drug effects/*physiology
MH  - Kidney Tubules, Collecting/drug effects/physiology
MH  - Kidney Tubules, Distal/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Nephrons/drug effects/*physiology
MH  - Patch-Clamp Techniques
MH  - Sodium, Dietary/pharmacology
EDAT- 2012/08/31 06:00
MHDA- 2013/01/25 06:00
CRDT- 2012/08/31 06:00
PHST- 2012/08/31 06:00 [entrez]
PHST- 2012/08/31 06:00 [pubmed]
PHST- 2013/01/25 06:00 [medline]
AID - ajprenal.00247.2012 [pii]
AID - 10.1152/ajprenal.00247.2012 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2012 Nov 1;303(9):F1289-99. doi: 
      10.1152/ajprenal.00247.2012. Epub 2012 Aug 29.