Role of potassium and chlorine channels in the regulation of thymocyte volume in rats

Kurbannazarova, Ranokon S.; Tashmukhamedov, B. A.; Sabirov, Ravshan Z.

doi:10.1007/s10517-008-0152-0

Cited by 9 publications

(10 citation statements)

References 10 publications

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“…5B) suggests that a single thymocyte may express several hundreds (∼500 in this particular cell) of VSOR anion channels. Our results would suggest that only a small fraction of them will be active during the GSH release experiment, supposedly because the cells will be restoring their volume by the regulatory volume decrease (RVD) mechanism, which is very prominent in these cells [25], [26]. In addition, swelling-induced membrane depolarization might also diminish the electrochemical driving force for GSH efflux.…”

Section: Discussionmentioning

confidence: 99%

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Volume-Sensitive Anion Channels Mediate Osmosensitive Glutathione Release from Rat Thymocytes

et al. 2013

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Glutathione (GSH) is a negatively charged tripeptide, which is a major determinant of the cellular redox state and defense against oxidative stress. It is assembled inside and degraded outside the cells and is released under various physiological and pathophysiological conditions. The GSH release mechanism is poorly understood at present. In our experiments, freshly isolated rat thymocytes were found to release GSH under normal isotonic conditions at a low rate of 0.82±0.07 attomol/cell/min and that was greatly enhanced under hypoosomotic stimulation to reach a level of 6.1±0.4 attomol/cell/min. The swelling-induced GSH release was proportional to the cell density in the suspension and was temperature-dependent with relatively low activation energy of 5.4±0.6 kcal/mol indicating a predominant diffusion mechanism of GSH translocation. The osmosensitive release of GSH was significantly inhibited by blockers of volume-sensitive outwardly rectifying (VSOR) anion channel, DCPIB and phloretin. In patch-clamp experiments, osmotic swelling activated large anionic conductance with the VSOR channel phenotype. Anion replacement studies suggested that the thymic VSOR anion channel is permeable to GSH− with the permeability ratio PGSH/PCl of 0.32 for influx and 0.10 for efflux of GSH. The osmosensitive GSH release was trans-stimulated by SLCO/OATP substrates, probenecid, taurocholic acid and estrone sulfate, and inhibited by an SLC22A/OAT blocker, p-aminohippuric acid (PAH). The inhibition by PAH was additive to the effect of DCPIB or phloretin implying that PAH and DCPIB/phloretin affected separate pathways. We suggest that the VSOR anion channel constitutes a major part of the γ-glutamyl cycle in thymocytes and, in cooperation with OATP-like and OAT-like transporters, provides a pathway for the GSH efflux from osmotically swollen cells.

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Section: Discussionmentioning

confidence: 99%

“…Cell isolation was performed as described previously [24]–[26]. Briefly, the 6–8 weeks old rats were anaesthetized with halothane or diethyl ether and painlessly euthanized by cervical dislocation; the thymi were dissected and carefully washed with an ice-cold Ringer solution.…”

Section: Methodsmentioning

confidence: 99%

Volume-Sensitive Anion Channels Mediate Osmosensitive Glutathione Release from Rat Thymocytes

et al. 2013

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“…Cell isolation was performed as described previously [13,14,38]. Briefly, the 6–8 weeks old mice were anaesthetized with halothane and painlessly euthanized by cervical dislocation; the thymi were dissected and carefully washed with an ice-cold Ringer solution.…”

Section: Methodsmentioning

confidence: 99%

“…Arrazola et al [12] and Soler et al [15] found that osmotic swelling-induced fluxes of K + and Cl − were tightly coupled and were efficiently inhibited by a selective blocker of the K-Cl cotransporter, [(dihydroindenyl)oxy] alkanoic acid (DIOA). However, in our previous pharmacological study, the RVD process in rat thymocytes was completely abolished by blockers of potassium channels and swelling-activated anion channels [14] suggesting involvement of ion channels rather than the coupled K-Cl cotransporter in thymocyte volume regulation under hypotonicity. Here, we provide direct evidence that cell swelling activates two types of the volume-regulated anion channels, the volume-sensitive outwardly rectifying (VSOR) Cl − channel and the maxi-anion channel; and only the VSOR channel is chiefly responsible for the anionic efflux during RVD in thymocytes and is sensitive to DIOA.…”

Section: Introductionmentioning

confidence: 97%

Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

Kurbannazarova

Bessonova

Okada

et al. 2011

IJMS

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Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR) chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd3+ ions but not by phloretin. Surprisingly, [(dihydroindenyl)oxy] alkanoic acid (DIOA), a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD) phase of cellular response to hypotonicity was mildly suppressed by Gd3+ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl− channels.

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“…For patch-clamping, the cells were cultured in suspension under mild stirring during 3-5 h. All animal experiments were conducted in accordance with the ARRIVE guidelines and approved by the Bioethics Committee of the Institute of Biophysics and Biochemistry. The isolation of thymic lymphocytes (thymocytes) was performed as described previously (Kurbannazarova et al, 2003(Kurbannazarova et al, , 2008(Kurbannazarova et al, , 2011Sabirov et al, 2013). Briefly, the 6-8 weeks old rats, kept in vivarium on an average diet, were anaesthetized with halothane or diethyl ether and painlessly euthanized by cervical dislocation.…”

Section: Cellsmentioning

confidence: 99%

Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel

Tsiferova¹,

Khamidova

Amonov

et al. 2019

European Pharmaceutical Journal

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The volume-sensitive outwardly rectifying anion channel (VSOR) is a key component of volume regulation system critical for cell survival in non-isosmotic conditions. The aim of the present study was to test the effects of four tannin extracts with defined compositions on cell volume regulation and VSOR. Preparation I (98% of hydrolysable tannins isolated from leaves of sumac Rhus typhina L.) and Preparation II (100% of hydrolysable tannins isolated from leaves of broadleaf plantain Plantago major L) completely and irreversibly abolished swelling-activated VSOR currents in HCT116 cells. Both preparations profoundly suppressed the volume regulation in thymocytes with half-maximal effects of 40.9 μg/ml and 12.3 μg/ml, respectively. The inhibition was more efficient at lower concentrations but reverted at higher doses due to possible non-specific membrane-permeabilizing activity. Preparations III and IV (54,7% and 54.3% of hydrolysable tannins isolated, respectively, from roots and aboveground parts of Fergana spurge Euphorbia ferganensis B.Fedtch) inhibited VSOR activity in a partially reversible manner and suppressed the volume regulation with substantially higher half-maximal doses of 270 and 278 μg/ml, respectively, with no secondary reversion at higher doses. Hydrolysable tannins represent a novel class of VSOR channel inhibitors with the capacity to suppress the cell volume regulation machinery.

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Role of potassium and chlorine channels in the regulation of thymocyte volume in rats

Cited by 9 publications

References 10 publications

Volume-Sensitive Anion Channels Mediate Osmosensitive Glutathione Release from Rat Thymocytes

Volume-Sensitive Anion Channels Mediate Osmosensitive Glutathione Release from Rat Thymocytes

Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel

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