Role of NKCC in BK channel-mediated net K<sup>+</sup>secretion in the CCD

Li, Wen; Schreck, Carlos; Coleman, Richard A.; Wade, James B.; Hernandez, Yubelka; Zavilowitz, Beth; Warth, Richard; Kleyman, Thomas R.; Satlin, Lisa M.

doi:10.1152/ajprenal.00347.2011

Cited by 48 publications

(37 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although PCs are responsible for K ϩ secretion mediated by ROMK, there is increasing evidence that BK channels in ICs are primarily responsible for FIKS (17,27,44,46,59,62,63,68,77,89,100). The findings that L-WNK1 and WNK4 both inhibit ROMK expression and activity, yet L-WNK1 and WNK4 exert different effects on BK channel expression and activity, present a conundrum.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to PCs, functional and immunoreactive BK channels are abundant in the apical membrane of ICs (17, 27, 44, 59, 62, 63, 68, 77, 100). These cells presumably sustain FIKS via basolateral Na ϩ -K ϩ -Cl Ϫ cotransporter-mediated K ϩ uptake (46), since they possess little basolateral Na ϩ -K ϩ -ATPase activity (3,8,63,71,78). In animals fed a high-K ϩ diet, net K ϩ secretion in the ASDN is markedly enhanced, along with an increase in ROMK expression in PCs and BK expression in ICs (44,59,64,94).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Webb

Carrisoza-Gaytán

Montalbetti

et al. 2016

American Journal of Physiology-Renal Physiology

Self Cite

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

Section: Discussionmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Apical ROMK channels are expressed in PCs and K + secretion through ROMK channels depends on electrogenic Na + transport. BK channels have been primarily detected in apical membrane of ICs (38,39), where basolateral Na-K-2Cl cotransporters (40,41) may provide a mechanism for K + uptake, thereby allowing K + secretion through these cells. It is unlikely that K + secretion occurs through excessive activity of ROMK in CCD of Atp6v1b1 -/-mice, since ENaC activity in this tubule segment is blocked, as indicated by our microperfusion data (see Figure 2A).…”

Section: Discussionmentioning

confidence: 99%

Renal β-intercalated cells maintain body fluid and electrolyte balance

Gueutin¹,

Vallet²,

Jayat³

et al. 2013

J. Clin. Invest.

111

116

View full text Add to dashboard Cite

Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt-and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1 -/-mice) displayed renal loss of NaCl, K + , and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) and the pendrin/Na + -driven chloride/ bicarbonate exchanger (pendrin/NDCBE) transport system was impaired. ENaC was appropriately increased in the medullary collecting duct, suggesting a localized inhibition in the cortex. We detected high urinary prostaglandin E 2 (PGE 2 ) and ATP levels in Atp6v1b1 -/-mice. Inhibition of PGE 2 synthesis in vivo restored ENaC protein levels specifically in the cortex. It also normalized protein levels of the large conductance calciumactivated potassium channel and the water channel aquaporin 2, and improved polyuria and hypokalemia in mutant mice. Furthermore, pharmacological inactivation of the proton pump in β-ICs induced release of PGE 2 through activation of calcium-coupled purinergic receptors. In the present study, we identified ATP-triggered PGE 2 paracrine signaling originating from β-ICs as a mechanism in the development of the hydroelectrolytic imbalance associated with dRTA. Our data indicate that in addition to principal cells, ICs are also critical in maintaining sodium balance and, hence, normal vascular volume and blood pressure.

show abstract

“…In this context, K + secretion is mediated by the luminal large-conductance Ca 2+ -activated K + channel (referred to as the BK channel) and the basolateral Na + /K + /2Cl -cotransporter (7,8). The findings that both individuals with Bartter syndrome as a result of ROMK loss-of-function mutations and mice lacking ROMK expression have robust renal K + secretion highlight the importance of this BK channel-mediated K + secretory pathway (9).…”

Section: Challenging Traditionmentioning

confidence: 99%