Vitamin C controls the cystic fibrosis transmembrane conductance …

Short Description
we report a unique function of vitamin C on the cystic fibrosis (CF) … apical airway surface to vitamin C stimulated the transepithelial Cl …

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Vitamin C controls the cystic fibrosis transmembrane
conductance regulator chloride channel
Horst Fischer, Christian Schwarzer, and Beate Illek*
Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609
Communicated by Bruce N. Ames, University of California, Berkeley, CA, December 16, 2003 (received for review October 29, 2003)
Vitamin C (L-ascorbate) is present in the respiratory lining fluid of
human lungs, and local deficits occur during oxidative stress. Here
we report a unique function of vitamin C on the cystic fibrosis (CF)
transmembrane conductance regulator (CFTR), a cAMP-dependent
Cl channel that regulates epithelial surface fluid secretion. Vitamin
C (100 M) induced the openings of CFTR Cl channels by increasing
its average open probability from 0 to 0.21 0.08, without a
detectable increase in intracellular cAMP levels. Exposure of the
apical airway surface to vitamin C stimulated the transepithelial Cl
secretion to 68% of forskolin-stimulated currents. The average
half-maximal stimulatory constant was 36.5 2.9 M, which
corresponds to physiological concentrations. When vitamin C was
instilled into the nasal epithelium of human subjects, it effectively
activated Cl transport in vivo. In CF epithelia, previous treatment of…