AJP - Cell Physiology, Vol 258, Issue 1 C132-C139, Copyright © 1990 by American Physiological Society
An alkaline pH-activated Cl(-)-anion exchanger regulates pH homeostasis in fibroblasts
P. Y. Lin, M. Ahluwalia and E. Gruenstein
Department of Molecular Genetics, University of Cincinnati College of Medicine, Ohio 45267-0524.
Alkalinization of the cytoplasm in human fibroblasts activates Cl- efflux.
The pathway of Cl- efflux is inhibited by
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or by removal of
Cl- from the extracellular medium, but it is insensitive to the
Cl(-)-cation cotransport inhibitor bumetanide. These data indicate that the
alkali-stimulated Cl- pathway is a Cl(-)-anion exchanger. One function of
this pathway appears to involve intracellular pH homeostasis. Thus, after
alkalinization of the cytoplasm, recovery of the pH to basal levels is
impaired by DIDS or by removal of HCO3- from the extracellular medium, but
it is unaffected by the Na(+)-H+ exchange inhibitor amiloride. Reports from
a number of laboratories, including our own, have described a biphasic
efflux of Cl- in which kinetics suggested the presence of two subcellular
Cl- compartments. The data presented in this study provide a mechanism to
explain this kinetic behavior. The biphasic Cl- efflux kinetics are the
result of a transient alkalinization of the cytoplasm associated with a
change in PCO2 as cells are transferred from the incubator to the bench top
for the efflux assay.
