Role of hβ<sub>1</sub>in activation of human mesangial BK channels by cGMP kinase

Kudlacek, Patrick E.; Pluznick, Jennifer L.; Ma, Rong; Padanilam, Babu J.; Sansom, Steven C.

doi:10.1152/ajprenal.00046.2003

Cited by 31 publications

(27 citation statements)

References 35 publications

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“…Flow-dependent K 1 secretion is mediated by the "big" or "maxi"-K + channel (BK), a large conductance potassium channel that is expressed in all segments of the distal nephron, including the DCT, CNT, and collecting duct. During states of increased distal tubule flow, shear stress along the DCT activates the channel, possibly by increasing intracellular calcium levels and enhancing intracellular nitric oxide production (72,73). Both of the intracellular signals could increase the BK's open probability and thereby enhance the rate of K 1 efflux into the tubular lumen.…”

Section: The Wnk-spak/osr1 Signaling Pathway and Nccmentioning

confidence: 99%

Distal Convoluted Tubule

Subramanya

Ellison

2014

Clinical Journal of the American Society of Nephrology

222

185

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The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice.

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Section: The Wnk-spak/osr1 Signaling Pathway and Nccmentioning

confidence: 99%

Distal Convoluted Tubule

Subramanya

Ellison

2014

Clinical Journal of the American Society of Nephrology

222

185

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“…The present study shows that BK␤1 localizes to the basolateral membrane of the CCD but not the CNT during low-Na ϩ diet conditions. The BK␣/␤1 channel is also located in mesangial cells (22), where it may be involved in regulating GFR with acute volume expansion (31) and influence sodium absorption. However, the finding that GFR was not different among the different genotypes on the low-Na ϩ diet and the finding that the plasma aldosterone levels were the same in WT and Kcnmb1 Ϫ/Ϫ on low-Na ϩ diets suggest that the BK␣/␤1 in these glomerular cells are not influencing sodium reabsorption.…”

Section: Kcnmb1mentioning

confidence: 99%

Role of BKβ1 in Na⁺ reabsorption by cortical collecting ducts of Na⁺-deprived mice

Grimm

Irsik

Liu

et al. 2009

American Journal of Physiology-Renal Physiology

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On a low-Na+ diet (LNa+), urinary Na+ loss is prevented by aldosterone-induced Na+ reabsorption through epithelial Na+ channels (ENaC) in the connecting tubules (CNT) and cortical collecting ducts (CCD). However, the mechanism whereby K+ loss is minimized and Na+ reabsorption is maximized in the face of a reduced lumen-to-bath Na+ gradient is not fully understood. The large-conductance calcium-activated potassium channel (BK)β1 subunit (gene: Kcnmb1), which has a role in K+ secretion in the CNT, is absent in the CCD in mice on a control diet. We hypothesized that BKα/β1 helps to maximize Na+ reabsorption during Na+ deficiency. With LNa+, the Na+ clearance of Kcnmb1-mutant mice ( Kcnmb1−/−) was 45% greater and the plasma Na+ concentration and osmolality were significantly reduced compared with wild-type mouse (WT) controls. On LNa+, Kcnmb1−/− exhibited exacerbated volume depletion (higher Hct and weight loss) compared with WT. LNa+, which did not affect the mean arterial blood pressure (MAP) of WT, significantly reduced MAP of Kcnmb1−/−. The plasma aldosterone concentration of Kcnmb1−/− on LNa+ was significantly elevated compared with Kcnmb1−/− on a control diet but was not different from WT on LNa+. Immunohistochemical staining revealed that BKα and BKβ1, which were absent in the principal cells (PCs) of the CCD, were localized on the basolateral membrane (BSM) of PCs of WT on LNa+. Moreover, BKα was absent from the BSM of PCs of Na+-deficient Kcnmb1−/−. We conclude that part of the mechanism to maximize Na+ reabsorption during Na+ deficiency is the placement of BKα/β1 channels in the BSM of CCD PCs.

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“…However, when expressed at higher levels, TRPC3 no longer formed a SOC but could be activated by receptor-coupled phospholipase C. Thus the native TRPC4 may be interacting with another endogenous protein that influences its properties. It is now known that several types of channels have accessory subunits that influence the biophysical, pharmacological, and regulatory properties of the pore-forming subunit (11,22). It will be interesting to determine whether TRPC channels are similarly influenced by accessory subunits.…”

Section: Expression Of Trpc Isoforms In MMCmentioning

confidence: 99%

TRPC4 forms store-operated Ca²⁺ channels in mouse mesangial cells

Wang¹,

Pluznick²,

Wei³

et al. 2004

American Journal of Physiology-Cell Physiology

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. TRPC4 forms store-operated Ca 2ϩ channels in mouse mesangial cells. Am J Physiol Cell Physiol 287: C357-C364, 2004. First published March 24, 2004 10.1152/ ajpcell.00068.2004.-Studies were performed to identify the molecular component responsible for store-operated Ca 2ϩ entry in murine mesangial cells (MMC). Because the canonical transient receptor potential (TRPC) family of proteins was previously shown to comprise Ca 2ϩ -selective and -nonselective cation channels in a variety of cells, we screened TRPC1-TRPC7 with the use of molecular methods and the fura 2 method to determine their participation as components of the mesangial store-operated Ca 2ϩ (SOC) channel. Using TRPCspecific primers and RT-PCR, we found that cultured MMC contained mRNA for TRPC1 and TRPC4 but not for TRPC2, TRPC3, TRPC5, TRPC6, and TRPC7. Immunocytochemical staining of MMC revealed predominantly cytoplasmic expression of TRPC1 and plasmalemmal expression of TRPC4. The role of TRPC4 in SOC was determined with TRPC4 antisense and fura 2 ratiometric measurements of intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i). SOC was measured as the increase in [Ca 2ϩ ]i after extracellular Ca 2ϩ was increased from Ͻ10 nM to 1 mM in the continued presence of thapsigargin. We found that TRPC4 antisense, which reduced plasmalemmal expression of TRPC4, inhibited SOC by 83%. Incubation with scrambled TRPC4 oligonucleotides did not affect SOC. Immunohistochemical staining identified expressed TRPC4 in the glomeruli of mouse renal sections. The results of RT-PCR performed to distinguish between TRPC4-␣ and TRPC4-␤ were consistent with expression of both isoforms in brain but with only TRPC4-␣ expression in MMC. These studies show that TRPC4-␣ may form the homotetrameric SOC in mouse mesangial cells.

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Role of hβ₁in activation of human mesangial BK channels by cGMP kinase

Cited by 31 publications

References 35 publications

Distal Convoluted Tubule

Distal Convoluted Tubule

Role of BKβ1 in Na⁺ reabsorption by cortical collecting ducts of Na⁺-deprived mice

TRPC4 forms store-operated Ca²⁺ channels in mouse mesangial cells

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Role of hβ1in activation of human mesangial BK channels by cGMP kinase

Cited by 31 publications

References 35 publications

Distal Convoluted Tubule

Distal Convoluted Tubule

Role of BKβ1 in Na+ reabsorption by cortical collecting ducts of Na+-deprived mice

TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells

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Role of hβ₁in activation of human mesangial BK channels by cGMP kinase

Role of BKβ1 in Na⁺ reabsorption by cortical collecting ducts of Na⁺-deprived mice

TRPC4 forms store-operated Ca²⁺ channels in mouse mesangial cells