Cystic Fibrosis, the CFTR, and Rectifying Cl- Channels
The human genetic disease cystic fibrosis is caused by a single defective gene on chromosome 7 that codes for a 1480 amino acid protein called the cystic fibrosis transmembrane conductance regulator (CFTR). The defect causes a profound reduction of C1- permeability in several tissues, which in turn impairs salt absorption and fluid secretion. A 25–80 pS, rectifying Cl-channel has been targeted as the exclusive or primary channel affected in CF. However, we have found no evidence for signifi cant activation or spontaneous activity of this channel in cell-attached patches of normal lymphoblasts or dog tracheal cells. However, in dog tracheal cells, we find lower conductance, linear C1- channels that are spontaneously active in unstimulated cells and may show increased activity in stimulated cells. Attempts to correlate the expression of mRNA for the CFTR protein in various types of cells with the presence of the rectifying C1- channel show a lack of correlation: i.e., depolarization-activated rectifying C1- channels have been found in excised, inside-out patches from all cell types that we have examined to date, but the CFTR mRNA has so far only been detected in a subset of epithelial cells.
KeywordsCystic Fibrosis Anion Channel Sweat Duct Cystic Fibro Ussing Chamber Experiment
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