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Transmembrane effects of intracellular chloride on the inhibitory potency of extracellular H/sup 2/DIDS

Journal Article · · J. Gen. Physiol.; (United States)
DOI:https://doi.org/10.1085/jgp.83.5.657· OSTI ID:5325698
The ping-pong model for the red cell anion exchange system postulates that the transport protein band 3 can exist in two different conformations, one in which the transport site faces the cytoplasm (E/sub i/) and another in which it faces the outside medium (E/sub o/). This model predicts that an increase in intracellular chloride should increase the fraction of sites in the outward-facing, unloaded form (E/sub o/). Since external H/sub 2/DIDS is a competitive inhibitor of chloride exchange that does not cross the membrane, it must bind only to the E/sub o/ form. Thus, an increase in E/sub o/ should cause an increase in H/sub 2/DIDS inhibition. When intracellular chloride was increased at constant extracellular chloride, the inhibitory potency of H/sub 2/DIDS rose, as predicted by the ping-pong model. This increase was not due to the concomitant changes in intracellular pH or membrane potential. When the chloride gradient was reversed, the inhibitory potency of H/sub 2/DIDS decreased, again in qualitative agreement with the ping-pong model. These data provide support for the ping-pong model and also demonstrate that chloride gradients can be used to change the orientation of the transport protein. 46 references, 8 figures, 3 tables.
Research Organization:
Hospital for Sick Children, Toronto, Ontario
OSTI ID:
5325698
Journal Information:
J. Gen. Physiol.; (United States), Journal Name: J. Gen. Physiol.; (United States) Vol. 83; ISSN JGPLA
Country of Publication:
United States
Language:
English