Regulation of BK-α expression in the distal nephron by aldosterone and urine pH

Wen, Duo; Cornelius, Ryan J.; Yuan, Ye; Sansom, Steven C.

doi:10.1152/ajprenal.00171.2013

Cited by 43 publications

(59 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For all experiments, mice (12-20 wk old) had full access to water and were fed with standard rodent diet (TD.7012, Harlan Laboratories, Indianapolis, IN). For acid loading experiments, 1.5% NH 4Cl (280 mM) and 1% sucrose were added in the drinking water (12,44) ϩ concentration ϫ plasma osmolality/plasma K ϩ concentration ϫ urine osmolality, where both urine and plasma K ϩ concentrations were measured by flame photometry, as previously described (41). Urine titratable acid (TA) and net acid (NA) concentrations were determined as previously described (8).…”

Section: Methodsmentioning

confidence: 99%

“…The plasma membrane fraction of the kidney cortex was isolated using the Minute Plasma Membrane Protein Isolation Kit (Invent Biotechnologies, Eden Prairie, MN) according to the manufacturer's instructions. The quality of the plasma membrane isolation was verified as de- scribed in our previous study (44). Western blot analysis was performed as previously described by our laboratory (44).…”

Section: Methodsmentioning

confidence: 99%

“…The quality of the plasma membrane isolation was verified as de- scribed in our previous study (44). Western blot analysis was performed as previously described by our laboratory (44). The primary antibodies were anti-NBCe2 antibody (custom rabbit polyclonal antibody targeted against the mouse COOH-terminus: MEGIPSD-PQNGIHC, diluted 1:500, Bethyl Laboratories, Montgomery, TX), anti-H ϩ -ATPase B1 (goat polyclonal, diluted 1:200, Santa Cruz Biotechnology, Dallas, TX), and anti-cadherin (goat polyclonal, diluted 1:500, Santa Cruz Biotechnology) with goat anti-rabbit IgG or donkey anti-goat IgG conjugated to horseradish peroxidase (diluted 1:10,000-1:20,000, Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

“…Fluorescent IHC analysis of kidney sections was performed as previously described (44). The antibody used was as follows: anti-H ϩ -ATPase B1 (goat polyclonal, diluted 1:200, Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Wen

Yuan

Cornelius

et al. 2015

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

In the present study, we report that a mouse model lacking the electrogenic Na ϩ -HCO 3 Ϫ cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H ϩ -ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K ϩ and Ca 2ϩ wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H ϩ -ATPase in the plasma membrane.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Wen

Yuan

Cornelius

et al. 2015

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, aldosterone likely has a role in increasing ROMK expression in this setting (92,105). However, it is still unclear whether aldosterone, as well as other factors, have roles in translating an increase in dietary K ϩ to an increase in BK expression in ICs (12,17,97).…”

mentioning

confidence: 99%

Cell-specific regulation of L-WNK1 by dietary K⁺

Webb

Carrisoza-Gaytán

Montalbetti

et al. 2016

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Flow-induced K+ secretion in the aldosterone-sensitive distal nephron is mediated by high-conductance Ca2+-activated K+ (BK) channels. Familial hyperkalemic hypertension (pseudohypoaldosteronism type II) is an inherited form of hypertension with decreased K+ secretion and increased Na+ reabsorption. This disorder is linked to mutations in genes encoding with-no-lysine kinase 1 (WNK1), WNK4, and Kelch-like 3/Cullin 3, two components of an E3 ubiquitin ligase complex that degrades WNKs. We examined whether the full-length (or “long”) form of WNK1 (L-WNK1) affected the expression of BK α-subunits in HEK cells. Overexpression of L-WNK1 promoted a significant increase in BK α-subunit whole cell abundance and functional channel expression. BK α-subunit abundance also increased with coexpression of a kinase dead L-WNK1 mutant (K233M) and with kidney-specific WNK1 (KS-WNK1), suggesting that the catalytic activity of L-WNK1 was not required to increase BK expression. We examined whether dietary K+ intake affected L-WNK1 expression in the aldosterone-sensitive distal nephron. We found a paucity of L-WNK1 labeling in cortical collecting ducts (CCDs) from rabbits on a low-K+ diet but observed robust staining for L-WNK1 primarily in intercalated cells when rabbits were fed a high-K+ diet. Our results and previous findings suggest that L-WNK1 exerts different effects on renal K+ secretory channels, inhibiting renal outer medullary K+ channels and activating BK channels. A high-K+ diet induced an increase in L-WNK1 expression selectively in intercalated cells and may contribute to enhanced BK channel expression and K+ secretion in CCDs.

show abstract