Cellular distribution of the potassium channel KCNQ1 in normal mouse kidney

Zheng, Wencui; Verlander, Jill W.; Lynch, I. Jeanette; Cash, Melanie N.; Shao, Jiahong; Stow, Lisa R.; Cain, Brian D.; Weiner, I. David; Wall, Susan M.; Wingo, Charles S.

doi:10.1152/ajprenal.00087.2006

Cited by 39 publications

(28 citation statements)

References 43 publications

(44 reference statements)

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“…C3H mice were obtained from The Jackson Laboratory (Bar Harbor, ME). Tissues from Black Swiss 129 mice were prepared for a previous study using the same methods described below (46). All animal use protocols were approved by the Institutional Animal Care and Use Committee and in accordance with the animal use guidelines of the American Physiological Society.…”

Section: Methodsmentioning

confidence: 99%

Basolateral expression of the ammonia transporter family member Rh C glycoprotein in the mouse kidney

Kim¹,

Verlander²,

Bishop³

et al. 2009

American Journal of Physiology-Renal Physiology

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Ammonia metabolism and transport are critical for acid-base homeostasis. The ammonia transporter family member Rh C glycoprotein (Rhcg) is expressed in distal renal tubular segments, and its expression is regulated in parallel with renal ammonia metabolism. However, there are inconsistencies in its reported subcellular distribution, with both apical and basolateral Rhcg reported in rat and human kidney and only apical expression in mouse kidney. Because the membrane location of Rhcg is critical for understanding its physiological role, we reassessed mouse Rhcg localization using refined immunolocalization methods. Two antibodies directed against different Rhcg-specific epitopes identified both apical and basolateral Rhcg immunolabel in mouse kidney. Immunogold electron microscopy both confirmed basolateral plasma membrane Rhcg expression and showed that apical immunolabel represented expression in both the apical plasma membrane and in subapical cytoplasmic vesicles. Immunoblots and Northern blots identified similar bands in Balb/c and C57BL/6 kidneys, suggesting basolateral Rhcg may result from alternative trafficking. Basolateral Rhcg intensity was strain dependent, with less basolateral Rhcg expression in the Balb/c mouse compared with the C57BL/6 mouse. In mice with collecting duct-specific Rhcg gene deletion, generated using Cre-loxP techniques, neither apical nor basolateral Rhcg immunolabel was identified in the collecting duct, confirming that basolateral Rhcg was the product of the same gene product as apical Rhcg. Although basolateral Rhcg expression differed between C57BL/6 and Balb/c mice, Rh B glycoprotein, which is exclusively basolateral, was expressed at similar levels in the two strains. We conclude that Rhcg is present in both the apical and basolateral plasma membrane in the mouse kidney, where it is likely to contribute to renal ammonia metabolism.

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Section: Methodsmentioning

confidence: 99%

Basolateral expression of the ammonia transporter family member Rh C glycoprotein in the mouse kidney

Kim¹,

Verlander²,

Bishop³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…Immunolocalization of Rhbg and Rhcg was accomplished using immunoperoxidase procedures and a commercially available kit (Mach2, Biocare Medical, Concord, CA) using techniques described in detail previously (33,44,51,55,59). Anti-Rhbg and anti-Rhcg antibodies were used at 1:2,000 and 1:30,000 dilution, respectively.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression

Kim

Baylis

Verlander

et al. 2007

American Journal of Physiology-Renal Physiology

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ID. Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression. Am J Physiol Renal Physiol 293: F1238-F1247, 2007. First published July 25, 2007; doi:10.1152/ajprenal.00151.2007.-Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na ϩ and K ϩ were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass. intercalated cell; principal cell; cortical collecting duct; outer medullary collecting duct REDUCED RENAL MASS IS ASSOCIATED with maintenance of fluid and electrolyte homeostasis until very substantial changes in glomerular filtration rate develop. For many components of fluid and electrolyte homeostasis, such as H 2 O, Na ϩ , and phosphate, homeostasis involves decreased tubular reabsorption that increases fractional excretion until there are appropriate rates of renal excretion. However, acid-base homeostasis requires fundamentally different mechanisms. Renal ammonia excretion, the predominant component of renal net acid excretion (10, 18, 42), does not depend on glomerular filtration of ammonia (37, 39). Instead, ammonia metabolism involves coordinated intrarenal ammonia production and epithelial segment transport (10,18,28). Thus maintenance of normal ammonia excretion in the presence of decreased nephron number associated with reduced renal mass requires adaptive changes in individual renal epithelial segment ammonia metabolism.Recent evidence suggests that the nonerythroid ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), are important for renal ammonia metabolism. Rhbg and Rhcg transport ammonia (2,36,60) and are expressed in the distal ...

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“…In the mouse kidney, KCNQ1 mRNA is expressed in the PT, DCT, CNT, CD, and glomeruli (Wang, 2004;Zheng et al, 2006). It is also distributed intensely and basolaterally in the DCT and CNT cells (Wang, 2004;Zheng et al, 2006), serving as part of the basolateral potassium channels (Hamilton and Devor, 2012). Recent research results have confirmed that KCNQ1-related potassium channels, which are highly expressed at the apical membrane of proximal convoluted tubule, underlie the K + reabsorption (Wang, 2004).…”

Section: Discussionmentioning

confidence: 96%

“…(Schroeder et al, 2000;Vallon et al, 2001Vallon et al, , 2005Warth et al, 2002;Lang et al, 2007;Yang et al, 2007;Das et al, 2009;Pan et al, 2010;Amin et al, 2012;Sung et al, 2014). In the mouse kidney, KCNQ1 mRNA is expressed in the PT, DCT, CNT, CD, and glomeruli (Wang, 2004;Zheng et al, 2006). It is also distributed intensely and basolaterally in the DCT and CNT cells (Wang, 2004;Zheng et al, 2006), serving as part of the basolateral potassium channels (Hamilton and Devor, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, KCNQ1 expression has been discovered in nephron segments of the kidney, including renal epithelia of the late proximal tubule (PT), distal convoluted tubule (DCT), connecting segment (CNT), collecting ducts (CD), and glomeruli (Wang, 2004;Zheng et al, 2006). It is likely to play a role in stabilizing the membrane potential of tubular cells and then regulating electrolyte reabsorption (Vallon et al, 2001(Vallon et al, , 2005Lang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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KCNQ1 A340E impairs electrolyte homeostasis independently of the renin-angiotensin-aldosterone system in mice

et al. 2016

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ABSTRACT. KCNQ1 (KvLQT1) is the pore-forming a-subunit of the potassium channel. To uncover its role in electrolyte metabolism, we investigated the effects of KCNQ1 A340E, a loss-of-function mutant, on J343 mice. Compared with the normal controls (C57BL/6J mice) bearing the wild-type KCNQ1 gene, J343 mice bearing KCNQ1 A340E demonstrated a much higher 24-h intake of electrolytes (potassium, sodium, and chloride). However, they suffered from significant electrolyte loss through both the feces and urine during a period of 24 h. Unbalance in electrolyte metabolism disrupted the electrolyte homeostasis in the J343 mice, which was characterized by the comparatively lower level of serum potassium (J343 vs C57BL/6J: 12.06 ± 1.47 vs 14.44 ± 3.58 mM, P = 0.01) and higher levels of serum sodium (J343 vs C57BL/6J: 148.05 ± 4.47 vs 115.15 ± 17.25 mM, P = 4.20 x 10 -4 ) and chloride (J343 vs C57BL/6J: 118.0 ± 4.47 vs 85.21 ± 11.90 mM, P = 2.47 x 10 -5 ). Between the J343 and C57BL/6J mice, there was no statistically significant difference in KCNQ1 expression in the gastrointestinal tract and kidney. Normal concentrations of plasma renin, angiotensin I, and aldosterone were also detected in both lines of mice. KCNQ1, therefore, is suggested to play a central role in electrolyte metabolism. KCNQ1 A340E, with the loss-of-function phenotype, may dysregulate electrolyte homeostasis in mice independently of the activity of the renin-angiotensin-aldosterone system.

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Cellular distribution of the potassium channel KCNQ1 in normal mouse kidney

Cited by 39 publications

References 43 publications

Basolateral expression of the ammonia transporter family member Rh C glycoprotein in the mouse kidney

Basolateral expression of the ammonia transporter family member Rh C glycoprotein in the mouse kidney

Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression

KCNQ1 A340E impairs electrolyte homeostasis independently of the renin-angiotensin-aldosterone system in mice

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