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⁺-C1^- 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: α-subunit (61%), β-subunit (41%), and γ-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.