Cytosolic Inhibition and Excision Activation of Epithelial Chloride Channels
Epithelial chloride channels with intermediate conductance (20–80 pS) have been identified in respiratory epithelia in primary culture (4,10,12, 13,19,21),in colonic carcinoma cells (9,11), sweat ducts (1,22), in the rectal gland of Squalus acan-thias (8) and in the thick ascending limb of Henle’s loop (6). The properties of these channels have recently been reviewed (5). In short, it appears likely that most of these channels share in common the following properties: They are activated by the cAMP pathway (7,16,17) and by proteinkinase C (12,15), and they are indirectly activated by increases in cytosolic Ca2+ activity (20,21). Furthermore, these channels are insensitive to cytosolic pH, ATP, and they are inhibited by chloride channel blockers such as NPPB, DIDS, amidine and indanylphenoxyacetic acids (2,14,18). In addition, it has been shown by several laboratories (3,13,19) that this type of chloride channel is absent in respiratory cells from cystic fibrosis (CF) patients, but that it appears when membrane patches from these cells are ripped off. This channel activation was caused by long lasting depolarization of excised membrane patches from CF cells (12,16, 17). On the other hand, we have shown more recently (13) that no depolarization was necessary for channel activation if, unlike the previous studies, excision was carried out not at room temperature but at 37°C.
KeywordsCystic Fibrosis Chloride Channel Clamp Voltage Rectal Gland Sweat Duct
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