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, sorbit ol, thymidine, choline, and K+ (Rb-86(+)) was investigated. For each s olute tested, reduction in the osmolality of the medium from 300 to 20 0 mosmol/kgH(2)O caused a significant increase in the unidirec tional influx rate. In each case, the osmotically activated transport compone nt was nonsaturable up to external substrate concentrations of 50 mM. Inhibitors of the swelling-activated anion channel of HeLa cells [quin ine, 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 eff lux of taurine and I-. Tamoxifen and NPPB were similarly effective at blocking the osmotically activated efflux of Rb-86(+). The simplest of several hypotheses consistent with the data is that the osmotically a ctivated transport of the different solutes tested here is via a swell ing-activated anion-selective channel that has a significant cation pe rmeability and a minimum pore diameter of 8-9 Angstrom.