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Cl/sup -/ transport pathways regulated by Ca/sup + +/, cAMP, and pH in human fibroblasts

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5856693

Under basal conditions Cl/sup -/ efflux from human fibroblasts occurs with a rate constant of permeability of 0.08 min/sup -1/. 50% of the basal efflux is due to Cl/sup -//anion exchange and is DIDS inhibitable, 25% is due to Na/sup +//K/sup +//Cl/sup -/ cotransport and is furosemide inhibitable, and 20% is due to an electrically conductive pathway. Increasing intracellular Ca/sup + +/ with A23187 stimulates Cl/sup -/ efflux by 30%. This increase appears to occur entirely via an electrically conducting pathway, but unlike basal Cl/sup -/ conductance, it is DIDS sensitive. Exposure of the cells to dibutyryl cAMP stimulates Cl/sup -/ efflux by 15%. They do not yet know whether the cAMP stimulated pathway is electrically conductive, but the stimulation is additive with that caused by elevated Ca/sup + +/ suggesting that different pathways are activated. Elevation of intracellular pH by any of several standard methods increases Cl/sup -/ efflux by as much as 700%. The pH effect appears to be mediated by a Cl/sup -//anion exchange pathway since it is DIDS sensitive and electroneutral. Previous work from this laboratory describing a transient rapid efflux of Cl/sup -/ followed by a slower efflux phase can now be explained as the result of a transient alkalinization of cells rather than as 2 subcellular Cl/sup -/ compartments. This alkalinization occurs when cells are transferred from a 5% CO/sub 2/ atmosphere during /sup 36/Cl/sup -/ load to ambient CO/sub 2/ for efflux.

Research Organization:
Univ. of Cincinnati, OH
OSTI ID:
5856693
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
Country of Publication:
United States
Language:
English