Regulation of chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia |
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| Authors: | M Li J D McCann M P Anderson J P Clancy C M Liedtke A C Nairn P Greengard M J Welsch |
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| Institution: | Laboratory of Membrane Transport, University of Iowa College of Medicine, Iowa City 52242. |
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| Abstract: | Apical membrane chloride channels control chloride secretion by airway epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis. In normal intact cells, activation of protein kinase C (PKC) by phorbol ester either stimulated or inhibited chloride secretion, depending on the physiological status of the cell. In cell-free membrane patches, PKC also had a dual effect: at a high calcium concentration, PKC inactivated chloride channels; at a low calcium concentration, PKC activated chloride channels. In cystic fibrosis cells, PKC-dependent channel inactivation was normal, but activation was defective. Thus it appears that PKC phosphorylates and regulates two different sites on the channel or on an associated membrane protein, one of which is defective in cystic fibrosis. |
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