Re. Forster et al., The effect of 4,4 '-diisothiocyanato-stilbene-2,2 '-disulfonate on CO2 permeability of the red blood cell membrane, P NAS US, 95(26), 1998, pp. 15815-15820
Citations number
26
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
It has long been assumed that the red cell membrane is highly permeable to
gases because the molecules of gases are small, uncharged, and soluble in l
ipids, such as those of a bilayer. The disappearance of (COO)-C-12-O-18-O-1
6 from a red cell suspension as the O-18 exchanges between labeled CO2 + HC
O3- and unlabeled HOH provides a measure of the carbonic anhydrase (CA) act
ivity (acceleration, or A) inside the cell and of the membrane self-exchang
e permeability to HCO3- (P-m,P-HCO3-) TO test this technique, we added suff
icient 4,4'-diisothiocyanato-stilbene-2,2'-disulfona (DIDS) to inhibit all
the HCO3-/Cl- transport protein (Band III or capnophorin) in a red cell sus
pension. We found that BIDS reduced P-m,P-HCO3- as expected, but also appea
red to reduce intracellular A, although separate experiments showed it has
no effect on CA activity in homogenous solution. A decrease in P-m,P-CO2 mo
uld explain this finding. With a more advanced computational model, which s
olves for CA activity and membrane permeabilities to both CO2 and HCO3-, we
found that DIDS inhibited both P-m,P-HCO3- and P-m,P-CO2, whereas intracel
lular CA activity remained unchanged. The mechanism by which DIDS reduces C
O2 permeability may not be through an action on the lipid bilayer itself, b
ut rather on a membrane transport protein, implying that this is a normal r
oute for at least part of red cell CO2 exchange.