Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin.

Research output: Contribution to journalJournal articlepeer-review

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Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. / Klausen, Thomas Kjaer; Hougaard, Charlotte; Hoffmann, Else K; Pedersen, Stine F.

In: American Journal of Physiology: Cell Physiology, Vol. 291, No. 4, 2006, p. C757-71.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Klausen, TK, Hougaard, C, Hoffmann, EK & Pedersen, SF 2006, 'Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin.', American Journal of Physiology: Cell Physiology, vol. 291, no. 4, pp. C757-71. https://doi.org/10.1152/ajpcell.00029.2006

APA

Klausen, T. K., Hougaard, C., Hoffmann, E. K., & Pedersen, S. F. (2006). Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. American Journal of Physiology: Cell Physiology, 291(4), C757-71. https://doi.org/10.1152/ajpcell.00029.2006

Vancouver

Klausen TK, Hougaard C, Hoffmann EK, Pedersen SF. Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. American Journal of Physiology: Cell Physiology. 2006;291(4):C757-71. https://doi.org/10.1152/ajpcell.00029.2006

Author

Klausen, Thomas Kjaer ; Hougaard, Charlotte ; Hoffmann, Else K ; Pedersen, Stine F. / Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. In: American Journal of Physiology: Cell Physiology. 2006 ; Vol. 291, No. 4. pp. C757-71.

Bibtex

@article{9db77a40a0f211dd86a6000ea68e967b,
title = "Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin.",
abstract = "The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P(2)] in this process. In Ehrlich-Lettre ascites (ELA) cells, a current with biophysical and pharmacological properties characteristic of VRAC was activated by hypotonic swelling. A 44% increase in cellular cholesterol content had no detectable effects on F-actin organization or VRAC activity. A 47% reduction in cellular cholesterol content increased cortical and stress fiber-associated F-actin content in swollen cells. Cholesterol depletion increased VRAC activation rate and maximal current after a modest (15%), but not after a severe (36%) reduction in extracellular osmolarity. The cholesterol depletion-induced increase in maximal VRAC current was prevented by F-actin disruption using latrunculin B (LB), while the current activation rate was unaffected by LB, but dependent on Rho kinase. Rho activity was decreased by approximately 20% in modestly, and approximately 50% in severely swollen cells. In modestly swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P(2) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part by preventing the hypotonicity-induced decrease in Rho activity and eliciting actin polymerization.",
author = "Klausen, {Thomas Kjaer} and Charlotte Hougaard and Hoffmann, {Else K} and Pedersen, {Stine F}",
note = "Keywords: Actins; Amides; Animals; Anions; Bicyclo Compounds, Heterocyclic; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Size; Chloride Channels; Cholesterol; Electric Conductivity; Enzyme Inhibitors; Hypotonic Solutions; Intracellular Signaling Peptides and Proteins; Ion Channels; Phosphatidylinositol Phosphates; Polymers; Protein-Serine-Threonine Kinases; Pyridines; Thiazoles; Thiazolidines; rho GTP-Binding Proteins; rho-Associated Kinases",
year = "2006",
doi = "10.1152/ajpcell.00029.2006",
language = "English",
volume = "291",
pages = "C757--71",
journal = "American Journal of Physiology: Cell Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "4",

}

RIS

TY - JOUR

T1 - Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin.

AU - Klausen, Thomas Kjaer

AU - Hougaard, Charlotte

AU - Hoffmann, Else K

AU - Pedersen, Stine F

N1 - Keywords: Actins; Amides; Animals; Anions; Bicyclo Compounds, Heterocyclic; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Size; Chloride Channels; Cholesterol; Electric Conductivity; Enzyme Inhibitors; Hypotonic Solutions; Intracellular Signaling Peptides and Proteins; Ion Channels; Phosphatidylinositol Phosphates; Polymers; Protein-Serine-Threonine Kinases; Pyridines; Thiazoles; Thiazolidines; rho GTP-Binding Proteins; rho-Associated Kinases

PY - 2006

Y1 - 2006

N2 - The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P(2)] in this process. In Ehrlich-Lettre ascites (ELA) cells, a current with biophysical and pharmacological properties characteristic of VRAC was activated by hypotonic swelling. A 44% increase in cellular cholesterol content had no detectable effects on F-actin organization or VRAC activity. A 47% reduction in cellular cholesterol content increased cortical and stress fiber-associated F-actin content in swollen cells. Cholesterol depletion increased VRAC activation rate and maximal current after a modest (15%), but not after a severe (36%) reduction in extracellular osmolarity. The cholesterol depletion-induced increase in maximal VRAC current was prevented by F-actin disruption using latrunculin B (LB), while the current activation rate was unaffected by LB, but dependent on Rho kinase. Rho activity was decreased by approximately 20% in modestly, and approximately 50% in severely swollen cells. In modestly swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P(2) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part by preventing the hypotonicity-induced decrease in Rho activity and eliciting actin polymerization.

AB - The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P(2)] in this process. In Ehrlich-Lettre ascites (ELA) cells, a current with biophysical and pharmacological properties characteristic of VRAC was activated by hypotonic swelling. A 44% increase in cellular cholesterol content had no detectable effects on F-actin organization or VRAC activity. A 47% reduction in cellular cholesterol content increased cortical and stress fiber-associated F-actin content in swollen cells. Cholesterol depletion increased VRAC activation rate and maximal current after a modest (15%), but not after a severe (36%) reduction in extracellular osmolarity. The cholesterol depletion-induced increase in maximal VRAC current was prevented by F-actin disruption using latrunculin B (LB), while the current activation rate was unaffected by LB, but dependent on Rho kinase. Rho activity was decreased by approximately 20% in modestly, and approximately 50% in severely swollen cells. In modestly swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P(2) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part by preventing the hypotonicity-induced decrease in Rho activity and eliciting actin polymerization.

U2 - 10.1152/ajpcell.00029.2006

DO - 10.1152/ajpcell.00029.2006

M3 - Journal article

C2 - 16687471

VL - 291

SP - C757-71

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

SN - 0363-6143

IS - 4

ER -

ID: 6768621