AJP - Cell Physiology, Vol 262, Issue 1 C32-C38, Copyright © 1992 by American Physiological Society
Reversed anion selectivity in cultured cystic fibrosis sweat duct cells
C. L. Bell, M. M. Reddy and P. M. Quinton
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
The human genetic disease cystic fibrosis (CF) is characterized by
defective epithelial Cl- conductance (GCl). To distinguish the CF-affected
GCl from other Cl- channels, we have studied the properties of GCl in
normal and CF cells grown from explanted reabsorptive sweat ducts (RD). The
cultured cells from normal subjects retained some of the typical duct cell
properties. The Na+ conductance inhibitor amiloride hyperpolarized
intracellular potentials (Vm) by 10.4 +/- 1.6 mV (n = 12). Substitution of
gluconate for Cl- depolarized Vm by 15.5 +/- 1.1 mV (n = 33). The apparent
GCl (G'Cl) of normal cells was sensitive to adenosine 3',5'-cyclic
monophosphate (forskolin, 10(-6) M), as evidenced by a significant increase
(63%, n = 9) in the Cl- gradient induced depolarization, and more selective
for Cl- than I- (substitution of Cl- by I- depolarized Vm by 6.3 +/- 0.3
mV, n = 49). Although the cells from CF subjects were statistically
indistinguishable from normal cells based on Vm (-18.5 +/- 1.2 mV, n = 49
vs. -20.1 +/- 1.8 mV, n = 28), CF cells expressed differences in G'Cl,
responses to forskolin, and anion selectivity. CF cells had a significantly
reduced G'Cl as indicated by blunted responses to imposed Cl- gradients
(26% of normal, n = 28). In contrast to our observations in normal cells,
the G'Cl of CF cells was insensitive to forskolin.(ABSTRACT TRUNCATED AT
250 WORDS)
