Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion

Turnheim, Klaus; Plass, Herbert; Wyskovsky, Wolfgang

doi:10.1016/s0005-2736(01)00456-4

Cited by 22 publications

(10 citation statements)

References 45 publications

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“…Acting in concert to the Na + -pump, highly selective basolateral channels allow the extrusion of K + that otherwise retained depolarize the membrane potential, hampering Na + -absorption. This is the case in the kidney and intestine where inhibition of basolateral K + channels reduced Na + -absorption and Na + -coupled metabolite uptake (Turnheim et al, 2002;Hebert et al, 2005;Vallon et al, 2005), further strengthening the role of K + channels on epithelial Na + homeostasis. We envisioned that Na + -absorption in the airways can be controlled through basolateral K + channels, but their role in electrolyte transport has not been profusely studied in this tissue (Bardou et al, 2009).…”

Section: Discussionmentioning

confidence: 82%

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Vega

Guequén

Philp

et al. 2020

Preprint

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Airway mucociliary clearance (MCC) is the main mechanism of lung defense keeping the airways free of infection and mucus obstruction. Airways surface liquid (ASL) volume, ciliary beating and mucus are central for proper MCC, and are critically regulated by sodium (Na + ) absorption and anion secretion. Impaired MCC is a key feature of muco-obstructive disease. The calcium-activated potassium (K + )channel KCa.3.1, encoded by the Kcnn4 gene, participates in intestinal ion secretion and previous studies showed that its activation increase Na + absorption in airway epithelia, suggesting that hyperpolarization induced by KCa3.1 was sufficient to drive Na + absorption.However, its role in airway epithelial function is not fully understood. We therefore aimed to elucidate the role of KCa3.1 in MCC in a genetically engineered mouse model. We show that KCa3.1 inhibition reduced Na + absorption in mouse and human airway epithelium. Furthermore, the genetic deletion of Kcnn4 enhanced cilia beating frequency (CBF) and MCC ex vivo and in vivo.Kcnn4 was silenced in the Scnn1b-transgenic mouse (Scnn1b tg/+ ), a model of muco-obstructive lung disease triggered by increased epithelial Na + -absorption, leading to improvements in MCC and reduction of Na + -absorption. KCa3.1 deletion did not change the amount of mucus but did reduce mucus adhesion, neutrophil infiltration and emphysema. Our data support that KCa3.1 inhibition attenuated muco-obstructive disease in the Scnn1b tg/+ mice. K + -channel modulation may be a novel therapeutic strategy to treat muco-obstuctive lung diseases.

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Section: Discussionmentioning

confidence: 82%

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Vega

Guequén

Philp

et al. 2020

Preprint

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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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“…4) included the introduction of the channel blocker TEA before Ba 2ϩ , given the relatively high selectivity of the former for BK channels (37). When added after A23187 plus EBIO ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Cl⁻ secretory effects of EBIO in the rabbit conjunctival epithelium

Alvarez¹,

Zamudio²,

Candia³

2005

American Journal of Physiology-Cell Physiology

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Experiments were conducted to determine whether the Cl- secretagogue, 1-ethyl-2-benzimidazolinone (EBIO), stimulates Cl- transport in the rabbit conjunctival epithelium. For this study, epithelia were isolated in an Ussing-type chamber under short-circuit conditions. The effects of EBIO on the short-circuit current (I(sc)) and transepithelial resistance (R(t)) were measured under physiological conditions, as well as in experiments with altered electrolyte concentrations. Addition of 0.5 mM EBIO to the apical bath stimulated the control I(sc) by 64% and reduced R(t) by 21% (P < 0.05; paired data). Under Cl(-)-free conditions, I(sc) stimulation using EBIO was markedly attenuated. In the presence of an apical-to-basolateral K+ gradient and permeabilization of the apical membrane, the majority of the I(sc) reflected the transcellular movement of K+ via basolateral K+ channels. Under these conditions, EBIO in combination with A23187 elicited nearly instantaneous 60-90% increases in I(sc) that were sensitive to the calmodulin antagonist calmidazolium and the K+ channel blocker tetraethyl ammonium. In the presence of an apical-to-basolateral Cl- gradient and nystatin permeabilization of the basolateral aspect, EBIO increased the Cl(-)-dependent I(sc), an effect prevented by the channel blocker glibenclamide (0.3 mM). The latter compound also was used to determine the proportion of EBIO-evoked unidirectional 36Cl- fluxes in the presence of the Cl- gradient that traversed the epithelium transcellularly. Overall, EBIO activated apical Cl- channels and basolateral K+ channels (presumably those that are Ca2+ dependent), thereby suggesting that this compound, or related derivatives, may be suitable as topical agents to stimulate fluid transport across the tissue in individuals with lacrimal gland deficiencies.

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Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion

Cited by 22 publications

References 45 publications

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Cl⁻ secretory effects of EBIO in the rabbit conjunctival epithelium

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Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion

Cited by 22 publications

References 45 publications

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Lack ofKcnn4improves mucociliary clearance in muco-obstructive lung disease

Silencing of hSlo potassium channels in human osteosarcoma cells promotes tumorigenesis

Cl− secretory effects of EBIO in the rabbit conjunctival epithelium

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Cl⁻ secretory effects of EBIO in the rabbit conjunctival epithelium