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• W1553673732 endingPage "2725" @default.
• W1553673732 startingPage "2718" @default.
• W1553673732 abstract "Cystic fibrosis (CF), the most common lethal genetic disease in Caucasians, is characterized by defective electrolyte transport in several epithelia. In sweat duct, pancreatic, intestinal, and airway epithelia, abnormalities in transepithelial ion transport may account for the manifestations of the disease. A Cl- impermeable apical cell membrane is a common feature in these CF epithelia. The rate of transepithelial Cl- transport is controlled in part by hormonally regulated apical membrane Cl- channels; in CF epithelia, Cl- channels are present but their regulation is defective. Most regulation studies have focused on an outwardly rectifying Cl- channel, although other channels may be involved in Cl- secretion. Phosphorylation of Cl- channels or associated regulatory proteins by cAMP-dependent protein kinase or by protein kinase C (at a low internal [Ca2+]) in excised patches of membrane activates Cl- channels in normal cells but not in CF cells. Phosphorylation with protein kinase C at a high internal [Ca2+] in excised patches of membrane inactivates the channel; such inactivation is normal in CF cells. Cl- channels can also be activated by other maneuvers including an increase in the cytosolic [Ca2+], sustained membrane depolarization, an increase in temperature, proteolysis, and changes in osmolarity; the response to such maneuvers is not defective in CF. In addition to the Cl- channel abnormalities, Na+ absorption is increased in CF epithelia. It is not certain whether the increased rate of Na+ absorption results from an increase in the number of cation channels or an alteration of their kinetics. The relation of these ion channel abnormalities to the CF gene product is unknown, but an understanding of the function of the protein product and its defective function in CF should yield important new insights into the pathogenesis and potential therapy of this disease." @default.
• W1553673732 created "2016-06-24" @default.
• W1553673732 creator A5043527770 @default.
• W1553673732 date "1990-07-01" @default.
• W1553673732 modified "2023-10-15" @default.
• W1553673732 title "Abnormal regulation of ion channels in cystic fibrosis epithelia" @default.
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• W1553673732 doi "https://doi.org/10.1096/fasebj.4.10.1695593" @default.
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