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+ (96Rb+) 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 swelling-activated 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 96Rb+. 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 A.
Hall
J A
JA
University Laboratory of Physiology, Oxford, United Kingdom.
Kirk
J
J
Potts
J R
JR
Rae
C
C
Kirk
K
K
D000838:Anions / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002412:Cations / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism*; D006801:Humans; D007455:Iodine / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009579:Nitrobenzoates / Q000494:pharmacology; D009994:Osmolar Concentration; D009995:Osmosis; D011188:Potassium / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013654:Taurine / Q000378:metabolism
D000838:Anions; D002412:Cations; D007473:Ion Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; D013654:Taurine; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D007455:Iodine; D011188:Potassium