Regulatory volume decrease in a renal distal tubular cell line (A6) I. Role of K+ and Cl−

Smet, Patrick De; Simaels, Jeannine; Driessche, Willy Van

doi:10.1007/bf01837407

Cited by 26 publications

(28 citation statements)

References 37 publications

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“…In these studies, transwell migration was undisturbed when Cl [29]. Our previous experiments demonstrated that incubation of cells in Cl --free solutions (gluconate-substituted solutions) can deplete intracellular Cl -, resulting in an inhibition of the volume-activated chloride current and a decrease of RVD capability [15].…”

Section: Discussionmentioning

confidence: 95%

Blockage of Volume-Activated Chloride Channels Inhibits Migration of Nasopharyngeal Carcinoma Cells

Mao

Wang²,

Fan

et al. 2007

Cell Physiol Biochem

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Cell migration is crucial for tumor metastasis. Membrane ion channels may play a major role in tumor cell migration because the cells must undergo changes in shape and volume during migration. In the present study, we used the transwell migration assay, an in vitro model for cell migration, and the patch-clamp technique to investigate the role of the volume-activated Cl^- current (I_cl,vol) in the regulation of the migration of nasopharyngeal carcinoma CNE-2Z cells. 5-Nitro-2- (3-phenylpropylamino) benzoic acid (NPPB) inhibited the I_cl,vol and the migration of CNE-2Z cells with almost identical dose-dependent pattern (IC₅₀ of 98.1 µM and 97.7 µM for I_cl,vol and cell migration, respectively). Extracellular adenosine triphosphate (ATP) also showed similar dose-dependent inhibitory effects on the currents and migration (IC₅₀ of 1.07mM, and 1.11mM for I_cl,vol and cell migration, respectively). Hypotonic treatments, which activated I_cl,vol, increased cell migration. Exposure to hypertonic solutions, which was shown to suppress I_cl,vol, inhibited cell migration. Replacement of Cl^- with gluconate, which is relatively chloride channel-impermeable, impaired cell migration, whereas substitution of Cl^- by I^- and Br^-, the chloride channel-permeable ions, did not significantly affect cell migration. Analysis of the effects of all the above treatments on I_cl,vol and cell migration indicated that the inhibition of migration was positively correlated with the blockage of I_cl,vol, with a correlation coefficient (r) of 0.97, suggesting a functional relationship between I_cl,vol and cell migration. These data suggest that the volume-activated Cl^- channels are involved in cell migration.

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Section: Discussionmentioning

confidence: 95%

Blockage of Volume-Activated Chloride Channels Inhibits Migration of Nasopharyngeal Carcinoma Cells

Mao

Wang²,

Fan

et al. 2007

Cell Physiol Biochem

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“…The methods used for this study are described in the accompanying paper [4]. Therefore, we restrict this section to those procedures and features which were not used in that study.…”

Section: Methodsmentioning

confidence: 99%

Regulatory volume decrease in a renal distal tubular cell line (A6) II. Effect of Na+ transport rate

1995

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A6 epithelia, a cell line originating from the distal tubular part of the kidney of Xenopus laevis, were cultured on permeable supports and mounted in an Ussing-type chamber. Cell thickness (Tc), short-circuit current (Isc) and transepithelial conductance (Gt) were recorded while tissues were bilaterally incubated in NaCl solutions and the transepithelial potential was clamped to zero. Effects of inhibition and stimulation of transepithelial Na+ transport on cell volume and on its regulation during a hyposmotic challenge were investigated. Under control conditions a slow spontaneous decrease of Tc described by a linear baseline was recorded. The reduction of the apical osmolality from 260 to 140 mosmol/kg did not alter cell volume significantly, demonstrating a negligible water permeability of the apical barrier. The inhibition of Na+ uptake by replacing apical Na+ by N-methyl-d-glucamine (NMDG+) did not affect cell volume under isotonic conditions. An increase of Tc by 12.1% above the control baseline was recorded after blocking active transport with ouabain for 60 min. The activation of Na+ transport with insulin or oxytocin, which is known to activate the apical water permeability in other epithelia, did not alter cell volume significantly. The insensitivity of cell volume to alterations in apical Na+uptake or Na+ pump rate confirms the close coupling between apical and basolateral transport processes. The blockage of basolateral K+ channels by 5 mM Ba2+ elicited a significant increase in Tc of 16.3% above control. Quinine, a potent blocker of volume-activated K+ channels, did not change Tc significantly. Basolateral hypotonicity elicited a rapid rise in Tc followed by a regulatory volume decrease (RVD). An RVD was also recorded after blocking apical Na+ uptake as well as after stimulating apical Na+ uptake with oxytocin or insulin. Inhibition of active transport with ouabain as well as blocking K+ efflux at the basolateral side with Ba2+ or quinine abolished the RVD. The inhibition of the RVD by ouabain seems to be caused by a depletion of cellular K+, whereas the effects of Ba2+ and quinine are most likely due to the blockage of the basolateral K+ pathway.

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“…Like many epithelial cells, renal cells are capable of regulating their volume in response to variations in external osmotic pressure (1)(2)(3). Briefly, cells respond to an increase in medium osmolarity by a process referred to as regulatory volume increase, whereas cells respond to the dilution of external medium by a regulatory volume decrease (RVD) 2 (4).…”

mentioning

confidence: 99%

“…Briefly, cells respond to an increase in medium osmolarity by a process referred to as regulatory volume increase, whereas cells respond to the dilution of external medium by a regulatory volume decrease (RVD) 2 (4). A variety of transport pathways have been implicated in both processes and result in rapid water flux across the plasma membrane, which causes cells to recuperate their initial volume correspondingly (5).…”

mentioning

confidence: 99%

Role of TASK2 in the Control of Apoptotic Volume Decrease in Proximal Kidney Cells

L’Hoste

Poët

Duranton

et al. 2007

Journal of Biological Chemistry

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Apoptotic volume decrease (AVD) is prerequisite to apoptotic events that lead to cell death. In a previous study, we demonstrated in kidney proximal cells that the TASK2 channel was involved in the K ؉ efflux that occurred during regulatory volume decrease. The aim of the present study was to determine the role of the TASK2 channel in the regulation of AVD and apoptosis phenomenon. For this purpose renal cells were immortalized from primary cultures of proximal convoluted tubules (PCT) from wild type and TASK2 knock-out mice (task2 ؊/؊ ). Apoptosis was induced by staurosporine, cyclosporin A, or tumor necrosis factor ␣. Cell volume, K ؉ conductance, caspase-3, and intracellular reactive oxygen species (ROS) levels were monitored during AVD. In wild type PCT cells the K ؉ conductance activated during AVD exhibited characteristics of TASK2 currents. In task2 ؊/؊ PCT cells, AVD and caspase activation were reduced by 59%. Whole cell recordings indicated that large conductance calcium-activated K ؉ currents inhibited by iberiotoxin (BK channels) partially compensated for the deletion of TASK2 K ؉ currents in the task2 ؊/؊ PCT cells. This result explained the residual AVD measured in these cells. In both cell lines, apoptosis was mediated via intracellular ROS increase. Moreover AVD, K ؉ conductances, and caspase-3 were strongly impaired by ROS scavenger N-acetylcysteine. In conclusion, the main K ؉ channels involved in staurosporine, cyclosporin A, and tumor necrosis factor-␣-induced AVD are TASK2 K ؉ channels in proximal wild type cells and iberiotoxin-sensitive BK channels in proximal task2 ؊/؊ cells. Both K ؉ channels could be activated by ROS production.

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Regulatory volume decrease in a renal distal tubular cell line (A6) I. Role of K+ and Cl−

Cited by 26 publications

References 37 publications

Blockage of Volume-Activated Chloride Channels Inhibits Migration of Nasopharyngeal Carcinoma Cells

Blockage of Volume-Activated Chloride Channels Inhibits Migration of Nasopharyngeal Carcinoma Cells

Regulatory volume decrease in a renal distal tubular cell line (A6) II. Effect of Na+ transport rate

Role of TASK2 in the Control of Apoptotic Volume Decrease in Proximal Kidney Cells

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