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

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.