In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 310, No. 1 ( 2016-01-01), p. F15-F26
Abstract:
Flow-induced K + secretion in the aldosterone-sensitive distal nephron is mediated by high-conductance Ca 2+ -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.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00226.2015
Language:
English
Publisher:
American Physiological Society
Publication Date:
2016
detail.hit.zdb_id:
1477287-5
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