Cystic fibrosis transmembrane conductance regulator-associated ATP and adenosine 3'-phosphate 5'-phosphosulfate channels in endoplasmic reticulum and plasma membranes.

Cystic fibrosis (CF) is characterized by abnormal regulation of epithelial ion and fluid transport due to mutations in the CF transmembrane conductance regulator (CFTR), an apical membrane-localized Cl- channel, that usually prevent it from exiting the endoplasmic reticulum. Defective or absent CFTR in the epithelium is believed to disrupt fluid balance in human airways and thereby contribute to chronic respiratory inflammation. Patch-clamp of the plasma membrane and outer membrane of the nuclear envelope of nuclei isolated from CFTR-expressing Chinese hamster ovary cells revealed that CFTR is associated with a regulated ATP channel in both membrane compartments. CFTR expression was also shown to be associated with permeability to another adenine nucleotide, adenosine 3'-phosphate 5'-phosphosulfate, the universal sulfate donor in cells. These results may provide a link between the ion channel function of CFTR and abnormal glycoprotein processing observed in CF.