Anion channel blockers inhibit swelling-activated anion, cation, and nonelectrolyte transport in HeLa cells

The effect of osmotic cell swelling on the permeability of HeLa cells to a range of structurally unrelated solutes including taurine, sorbitol, thymidine, choline, and K⁺ (⁸⁶Rb⁺) was investigated. For each solute tested, reduction in the osmolality of the medium from 300 to 200 mosmol/kgH₂O caused a significant increase in the unidirectional influx rate. In each case, the osmotically activated transport component was nonsaturable up to external substrate concentrations of 50 mM. Inhibitors of the swellingactivated anion channel of HeLa cells [quinine, 4,4'- diisothiocyanostilbene-2,2'-disulfonic acid, niflumate, 1,9- dideoxyforskolin, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), and tamoxifen] blocked the osmotically activated influx of each of the different substrates tested, as well as the osmotically activated efflux of taurine and I^-. Tamoxifen and NPPB were similarly effective at blocking the osmotically activated efflux of ⁸⁶Rb⁺. The simplest of several hypotheses consistent with the data is that the osmotically activated transport of the different solutes tested here is via a swelling-activated anion-selective channel that has a significant cation permeability and a minimum pore diameter of 8-9 Å.