The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1

A. J. Nicholl, J. Killey, M. N. Leonard, C. Garner

Research output: Contribution to journalArticle

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Abstract

This study investigates the mechamsms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO3 --buffered hypotonic solutions. Inhibition of RVD by 10 μM tamoxifen and 100 μM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA+ (inhibitor of K+ channels) indicates a role for these channels. In HCO3 --buffered Cl--free solutions RVD was partially abolished indicating that HCO3 - efflux can support RVD but also may have another role. Further experiments investigated whether HCO3 - assists in the accumulation of Cl- via Cl--HCO3 - exchange. Regulatory volume increase (RVI) was also HCO3 --dependent and was inhibited by 500 μM DIDS and 10 μM 5-(N,N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl--HCO3 - and Na+-H+exchange. Finally, in the presence of 10 μM DMA, RVD was partially inhibited providing further evidence for a role of Cl--HCO3 - exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K+ channels. RVD is HCO3 --dependent and HCO3 - efflux through VRAC appears to contribute directly to RVD. HCO3 -, however, also has another role in facilitating Cl- accumulation via Cl--HCO3 - exchange.

LanguageEnglish
Pages875-881
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume443
Issue number5-6
DOIs
Publication statusPublished - 2002

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Hypotonic Solutions
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Bicarbonates
Cells
Breast Neoplasms
HEPES
Cell Line
Osmotic Pressure
Tamoxifen
Cell Size
Anions
Chemical activation
Imaging techniques
Experiments
5-dimethylamiloride

Cite this

@article{b69df5fa9cb14d2e9e88ef4dfc7b29e1,
title = "The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1",
abstract = "This study investigates the mechamsms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO3 --buffered hypotonic solutions. Inhibition of RVD by 10 μM tamoxifen and 100 μM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA+ (inhibitor of K+ channels) indicates a role for these channels. In HCO3 --buffered Cl--free solutions RVD was partially abolished indicating that HCO3 - efflux can support RVD but also may have another role. Further experiments investigated whether HCO3 - assists in the accumulation of Cl- via Cl--HCO3 - exchange. Regulatory volume increase (RVI) was also HCO3 --dependent and was inhibited by 500 μM DIDS and 10 μM 5-(N,N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl--HCO3 - and Na+-H+exchange. Finally, in the presence of 10 μM DMA, RVD was partially inhibited providing further evidence for a role of Cl--HCO3 - exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K+ channels. RVD is HCO3 --dependent and HCO3 - efflux through VRAC appears to contribute directly to RVD. HCO3 -, however, also has another role in facilitating Cl- accumulation via Cl--HCO3 - exchange.",
keywords = "Cl-HCO exchange, HCO, K channels, RVD, Volume-regulated anion channels, ZR-75-1 cells",
author = "Nicholl, {A. J.} and J. Killey and Leonard, {M. N.} and C. Garner",
year = "2002",
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journal = "Pflugers Archiv European Journal of Physiology",
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The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1. / Nicholl, A. J.; Killey, J.; Leonard, M. N.; Garner, C.

In: Pflugers Archiv European Journal of Physiology, Vol. 443, No. 5-6, 2002, p. 875-881.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1

AU - Nicholl, A. J.

AU - Killey, J.

AU - Leonard, M. N.

AU - Garner, C.

PY - 2002

Y1 - 2002

N2 - This study investigates the mechamsms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO3 --buffered hypotonic solutions. Inhibition of RVD by 10 μM tamoxifen and 100 μM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA+ (inhibitor of K+ channels) indicates a role for these channels. In HCO3 --buffered Cl--free solutions RVD was partially abolished indicating that HCO3 - efflux can support RVD but also may have another role. Further experiments investigated whether HCO3 - assists in the accumulation of Cl- via Cl--HCO3 - exchange. Regulatory volume increase (RVI) was also HCO3 --dependent and was inhibited by 500 μM DIDS and 10 μM 5-(N,N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl--HCO3 - and Na+-H+exchange. Finally, in the presence of 10 μM DMA, RVD was partially inhibited providing further evidence for a role of Cl--HCO3 - exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K+ channels. RVD is HCO3 --dependent and HCO3 - efflux through VRAC appears to contribute directly to RVD. HCO3 -, however, also has another role in facilitating Cl- accumulation via Cl--HCO3 - exchange.

AB - This study investigates the mechamsms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO3 --buffered hypotonic solutions. Inhibition of RVD by 10 μM tamoxifen and 100 μM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA+ (inhibitor of K+ channels) indicates a role for these channels. In HCO3 --buffered Cl--free solutions RVD was partially abolished indicating that HCO3 - efflux can support RVD but also may have another role. Further experiments investigated whether HCO3 - assists in the accumulation of Cl- via Cl--HCO3 - exchange. Regulatory volume increase (RVI) was also HCO3 --dependent and was inhibited by 500 μM DIDS and 10 μM 5-(N,N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl--HCO3 - and Na+-H+exchange. Finally, in the presence of 10 μM DMA, RVD was partially inhibited providing further evidence for a role of Cl--HCO3 - exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K+ channels. RVD is HCO3 --dependent and HCO3 - efflux through VRAC appears to contribute directly to RVD. HCO3 -, however, also has another role in facilitating Cl- accumulation via Cl--HCO3 - exchange.

KW - Cl-HCO exchange

KW - HCO

KW - K channels

KW - RVD

KW - Volume-regulated anion channels

KW - ZR-75-1 cells

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U2 - 10.1007/s00424-001-0771-z

DO - 10.1007/s00424-001-0771-z

M3 - Article

VL - 443

SP - 875

EP - 881

JO - Pflugers Archiv European Journal of Physiology

T2 - Pflugers Archiv European Journal of Physiology

JF - Pflugers Archiv European Journal of Physiology

SN - 0031-6768

IS - 5-6

ER -