Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats.
The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na+ transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na+/H+ exchanger (NHE3), Na+ - K+-ATPase, the bumetanide-sensitive Na+ - K+ - 2Cl- cotransporter (BSC-1), the thiazide-sensitive Na+ - Cl- cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na+ loss and/or to maintain intracellular pH levels.
Elkjaer
Marie-Louise
ML
The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark.
Kwon
Tae-Hwan
TH
Wang
Weidong
W
Nielsen
Jakob
J
Knepper
Mark A
MA
Frøkiaer
Jørgen
J
Nielsen
Søren
S
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001769:Blood / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011141:Polyuria / Q000209:etiology; D011188:Potassium / Q000097:blood / Q000652:urine; D011191:Potassium Deficiency / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*; D012964:Sodium / Q000097:blood / Q000652:urine; D015222:Sodium Channels / Q000378:metabolism*; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D014556:Urine / Q000737:chemistry
D001639:Bicarbonates; D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; C578876:Slc12a3 protein, rat; C000613387:Slc9a3 protein, rat; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D000450:Aldosterone; D012964:Sodium; D011188:Potassium