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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

By A.J. Nicholl, Jennifer Killey, M.N. Leonard and C. Garner

Abstract

This study investigates the mechanisms 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

Topics: QP
Publisher: Springer-Verlag
Year: 2002
OAI identifier: oai:eprints.hud.ac.uk:9291
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