BK channels in the kidney: role in K<sup>+</sup>secretion and localization of molecular components

Pluznick, Jennifer L.; Sansom, Steven C.

doi:10.1152/ajprenal.00118.2006

Cited by 89 publications

(72 citation statements)

References 111 publications

(166 reference statements)

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“…Indeed, our group recently demonstrated that genetic ablation of TRPV4 abolishes flow-dependent [Ca 2ϩ ] i responses in microdissected distal nephron preparations (12). Consistently, flow-dependent K ϩ secretion in the distal nephron, a Ca 2ϩ -dependent process utilizing the maxi-K channel (13,14), is absent in TRPV4 knock-out animals (15).…”

Section: ؉mentioning

confidence: 85%

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Mamenko

Zaika

Boukelmoune

et al. 2013

Journal of Biological Chemistry

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Background: TRPV4 mediates flow-induced [Ca 2ϩ ] i responses in distal nephron cells. Results: Activation of PKC augments TRPV4-mediated responses to flow. Activation of PKA promotes TRPV4 translocation to the apical membrane. Conclusion: TRPV4 activity and TRPV4 trafficking are under discrete but synergistic control of PKC-and PKA-dependent pathways. Significance: Systemic physiological stimuli may affect TRPV4-mediated mechanosensitivity in the distal nephron via PKAand PKC-dependent mechanisms.

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Section: ؉mentioning

confidence: 85%

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Mamenko

Zaika

Boukelmoune

et al. 2013

Journal of Biological Chemistry

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“…27 Interestingly, in many cells, BK channels are described to control different steps of the secretary process. 9,[28][29][30] These observations prompted us to investigate whether BK channels could control the tumor growth through a modulation of chemokine expression (Fig. 4).…”

Section: Bk Channels Modulate Ccl2 and Ccl20 Chemokine Expression In mentioning

confidence: 99%

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Cambien

Rezzonico

Vitale

et al. 2008

Intl Journal of Cancer

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Potassium channels, the most diverse superfamily of ion channels, have recently emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large conductance Ca 21 -activated K 1 channels, often referred to as BK channels, are at the crossroads of several tumor-associated processes such as cell proliferation, survival, secretion and migration. Despite the high BK channel expression in osteosarcoma (OS), their function has not yet been investigated in this malignant bone pathology. Here, using stable RNA interference to reduce the expression of hSlo, the human pore-forming a-subunit of the BK channel, in human Cal72 OS cells, we show that BK channels play a functional role in carcinogenesis. Our results reveal for the first time that BK channels exhibit antitumoral properties in OS in vivo and affect the tumor microenvironment through the modulation of both chemokine expression and leukocyte infiltration. ' 2008 Wiley-Liss, Inc.Key words: osteosarcoma; ion channels; xenografts; chemokines; tumor microenvironmentThe development of cancer is a multistep process that usually occurs over many decades. This process encompasses the alteration of genes and/or proteins involved in fundamental cellular mechanisms like proliferation, apoptosis and differentiation. There is mounting evidence pointing to the involvement of ion channels in cancer progression. 1 The most compelling evidence regarding the involvement of ion channels in the transformation process relates to the over-expression of voltage-gated K channels in a variety of cancers. Among them are the large conductance Ca 21 -activated K 1 channels, often referred to as BK channels (for Big K). Indeed, we and others have shown that BK channels are a unique class of ion channels that are activated by a change in intracellular calcium, in voltage 2 and by a wide variety of molecules and molecular mechanisms including growth factors and hypoxia that, interestingly, are involved in carcinogenesis. [3][4][5][6] BK channels are expressed in a broad spectrum of cells in which they play a crucial role in neurotransmitter release, muscle relaxation 7,8 and diverse activities involved in tumor-associated processes such as cell proliferation, survival, secretion and migration. [9][10][11] Importantly, in human glioma, BK channels are significantly up-regulated, and their expression levels seem to correlate positively with tumor grade and poor patient prognosis. In vitro studies have suggested a role for BK channels in the control of glioma cell growth, survival and migration. 4,11 In addition glioma, we have shown a high level of BK expression in osteosarcoma (OS). 12 Altogether, these studies suggest an important role for BK in carcinogenesis and point to its potential value as a prognostic marker and/or a therapeutic target. To date, however, none of these aspects have been addressed in vivo.OS is the most common malignant bone tumor in children and adolescents. 13 OS is characterized by a hig...

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“…In the ASDN, K + is taken up by basolateral Na + /K + -ATPases and is excreted by luminal renal outer medullary K + (ROMK) and large conductance Ca 2+ -activated K + (BK) channels. 2,[7][8][9] The electrochemical driving force for K + secretion is provided by activation of apical epithelial Na + channels (ENaCs). 1,10 In the ASDC, K + is taken up across the basolateral plasma membrane by the Na -cotransporter type 1.…”

mentioning

confidence: 99%

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Todkar

Picard²,

Loffing‐Cueni³

et al. 2015

Journal of the American Society of Nephrology

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Aldosterone-independent mechanisms may contribute to K + homeostasis. We studied aldosterone synthase knockout (AS 2/2 ) mice to define renal control mechanisms of K + homeostasis in complete aldosterone deficiency. AS 2/2 mice were normokalemic and tolerated a physiologic dietary K + load (2% K + , 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K + intake (5% K + ), AS 2/2 mice decompensated and became hyperkalemic. High-K + diets induced upregulation of the renal outer medullary K + channel in AS 2/2 mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K + excretion was detected only with a 2% K + diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS 2/2 mice than in AS +/+ mice and was downregulated in mice of both genotypes in response to increased K + intake.Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS 2/2 mice. In contrast with the kidney, the distal colon of AS 2/2 mice did not respond to dietary K + loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K + load can be achieved in aldosterone deficiency by aldosteroneindependent activation of the renal outer medullary K + channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K + secretion and increased intratubular availability of Na + that can be reabsorbed in exchange for K + secreted.

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BK channels in the kidney: role in K⁺secretion and localization of molecular components

Cited by 89 publications

References 111 publications

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

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BK channels in the kidney: role in K+secretion and localization of molecular components

Cited by 89 publications

References 111 publications

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

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BK channels in the kidney: role in K⁺secretion and localization of molecular components