AJP - Cell Physiology, Vol 255, Issue 4 C552-C558, Copyright © 1988 by American Physiological Society
Regulation of conductive Cl- transport in human fibroblasts
P. Lin, M. Ahluwalia and E. Gruenstein
Department of Biochemistry and Molecular Biology, University of Cincinnati College of Medicine, Ohio 45267-0522.
Under normal growth conditions, approximately 20% of the efflux of Cl- from
human fibroblasts occurs via an electrically conductive pathway or Cl-
channel. This basal Cl- conductance is insensitive to the Cl- -anion
exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
and to the Cl- -cation cotransport inhibitor bumetanide. Exposure of the
cells to dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) for 15 min
increases the electrically conductive component of Cl- efflux by
approximately 20%. Unlike the basal Cl- conductance, the cAMP-activated
channel is DIDS sensitive, indicating that cAMP activates a different Cl-
pathway from the one responsible for the basal Cl- conductance. Elevation
of intracellular Ca2+ by addition of the ionophore A23187 also stimulates
Cl- efflux via a DIDS inhibitable, electrically conductive Cl- pathway.
That the cAMP- and Ca2+-stimulated pathways are different is suggested by
the observation that simultaneous exposure of cells to optimal levels of
dibutyryl cAMP and A23187 results in an increased Cl- efflux equal to the
sum of the two factors acting independently. Prostaglandin E1, a known
activator of adenylate cyclase, also elevates the levels of intracellular
free Ca2+ in these cells and concomitantly activates both the cAMP- and the
Ca2+-stimulated Cl- channels. Although regulated, Cl- channels are known to
function in the modulation of nerve and muscle excitability, their role in
fibroblast function is not clear.
