Transport of organic substrates via a volume-activated channel.
We have investigated the volume-activated transport of organic solutes in flounder erythrocytes. Osmotic swelling of cells suspended in a Na(+)-free medium led to increased membrane transport of taurine, glucose, and uridine. For each compound there was a significant lag period (1-2 min at 10 degrees C) between cell swelling and activation of the flux. The volume-activated fluxes of each of the substrates increased in parallel with increasing cell volume, and those of taurine and uridine increased linearly with concentration (up to 19 mM). The volume-activated fluxes of each of the three compounds showed similar sensitivities to a number of anion-selective channel blockers (5-nitro-2-(3-phenylpropylamino)benzoic acid > 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid approximately MK-196 > niflumic acid > furosemide); the IC50 for the inhibition of the volume-activated fluxes by NPPB was around 12 microM. The results are consistent with the hypothesis that the volume-activated transport of organic osmolytes is via a pathway with the characteristics of a volume-activated "chloride channel." This raises the question of whether the transport of organic substrates might represent a physiological role for such channels in other cell types.
Kirk
K
K
University Laboratory of Physiology, Oxford, United Kingdom.
Ellory
J C
JC
Young
J D
JD
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D018118:Chloride Channels; D004232:Diuretics / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005432:Flounder; D005665:Furosemide / Q000494:pharmacology; D007038:Hypotonic Solutions; D007189:Indans / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D013654:Taurine / Q000097:blood*; D014529:Uridine / Q000097:blood*
D001786:Blood Glucose; D018118:Chloride Channels; D004232:Diuretics; D007038:Hypotonic Solutions; D007189:Indans; D007473:Ion Channels; D008565:Membrane Proteins; D009579:Nitrobenzoates; D013654:Taurine; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; D005665:Furosemide; C013352:indacrinone; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D014529:Uridine