| First Author | Wen D | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 4 | Pages | F463-76 |
| PubMed ID | 23761673 | Mgi Jnum | J:200818 |
| Mgi Id | MGI:5509385 | Doi | 10.1152/ajprenal.00171.2013 |
| Citation | Wen D, et al. (2013) Regulation of BK-alpha expression in the distal nephron by aldosterone and urine pH. Am J Physiol Renal Physiol 305(4):F463-76 |
| abstractText | In the distal nephron, the large-conductance Ca-activated K (BK) channel, comprised of a pore-forming-alpha (BK-alpha) and the BK-beta4 subunit, promotes K excretion when mice are maintained on a high-K alkaline diet (HK-alk). We examined whether BK-beta4 and the acid-base status regulate apical membrane expression of BK-alpha in the cortical (CCD) and medullary collecting ducts (MCD) using immunohistochemical analysis (IHC) and Western blot. With the use of IHC, BK-alpha of mice on acontrol diet localized mostly cytoplasmically in intercalated cells (IC) of the CCD and in the perinuclear region of both principle cells (PC) and IC of the MCD. HK-alk wild-type mice (WT), but not BK-beta4 knockout mice (beta4KO), exhibited increased apical BK-alpha in both the CCD and MCD. When given a high-K acidic diet (HK-Cl), BK-alpha expression increased but remained cytoplasmic in the CCD and perinuclear in the MCD of both WT and beta4KO. Western blot confirmed that total BK-alpha expression was enhanced by either HK-alk or HK-Cl but only increased in the plasma membrane with HK-alk. Compared with controls, mice drinking NaHCO3 water exhibited more apical BK-alpha and total cellular BK-beta4. Spironolactone given to mice on HK-alk significantly reduced K secretion and decreased total cellular BK-alpha but did not affect cellular BK-beta4 and apical BK-alpha. Experiments with MDCK-C11 cells indicated that BK-beta4 stabilizes surface BK-alpha by inhibiting degradation through a lysosomal pathway. These data suggest that aldosterone mediates a high-K-induced increase in BK-alpha and urinary alkalinization increases BK-beta4 expression, which promotes the apical localization of BK-alpha. |
