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Regulation of conductive Cl sup minus transport in human fibroblasts

Journal Article · · American Journal of Physiology; (USA)
OSTI ID:6037301
; ;  [1]
  1. Univ. of Cincinnati College of Medicine, OH (USA)

Under normal growth conditions, {approximately}20% of the efflux of {sup 36}Cl{sup {minus}} from human fibroblasts occurs via an electrically conductive pathway or Cl{sup {minus}} channel. This basal Cl{sup {minus}} conductance is insensitive to the Cl{sup {minus}}-anion exchange inhibitor 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (DIDS) and to the Cl{sup {minus}}-cation cotransport inhibitor bumetanide. Exposure of the cells to dibutyryl adenosine 3{prime},5{prime}-cyclic monosphosphate (cAMP) for 15 min increases the electrically conductive component of {sup 36}Cl{sup {minus}} efflux by {approximately}20%. Unlike the basal Cl{sup {minus}} conductance, the cAMP-activated channel is DIDS sensitive, indicating that cAMP activates a different Cl{sup {minus}} pathway from the one responsible for the basal Cl{sup {minus}} conductance. Elevation of intracellular Ca{sup 2+} by addition of the ionophore A23187 also stimulates {sup 36}Cl{sup {minus}} efflux via a DIDS inhibitable, electrically conductive Cl{sup {minus}} pathway. That the cAMP- and Ca{sup 2+}-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{sup {minus}} efflux equal to the sum of the two factors acting independently. Prostaglandin E{sub 1}, a known activator of adenylate cyclase, also elevates the levels of intracellular free Ca{sup 2+} in these cells and concomitantly activates both the cAMP- and the Ca{sup 2+}-stimulated Cl{sup {minus}} channels. Although regulated, Cl{sup {minus}} channels are known to function in the modulation of nerve and muscle excitability, their role in fibroblast function is not clear.

OSTI ID:
6037301
Journal Information:
American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:4; ISSN 0002-9513; ISSN AJPHA
Country of Publication:
United States
Language:
English