The CLIC1 Chloride Channel Is Regulated by the Cystic Fibrosis Transmembrane Conductance Regulator when Expressed in Xenopus Oocytes |
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Authors: | John C Edwards |
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Institution: | (1) UNC Kidney Center and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina |
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Abstract: | CLIC proteins comprise a family of chloride channels whose physiological roles are uncertain. To gain further insight into
possible means of CLIC1 channel activity regulation, this protein was expressed in Xenopus oocytes alone or in combination with the cystic fibrosis transmembrane conductance regulator (CFTR). Whole-cell currents
were determined using two-electrode voltage-clamp methods. Expression of CLIC1 alone did not increase whole-cell conductance
either at rest or in response to increased intracellular cyclic adenosine monophosphate (cAMP). However, expression of CLIC1
with CFTR led to increased cAMP-activated whole-cell currents compared to expression from the same amount of CFTR mRNA alone.
IAA-94 is a drug known to inhibit CLIC family channels but not CFTR. In oocytes expressing both CLIC1 and CFTR, a fraction
of the cAMP-activated whole-cell current was sensitive to IAA-94, whereas in oocytes expressing CFTR alone, the cAMP-stimulated
current was resistant to the drug. Cell fractionation studies revealed that the presence of CFTR conferred cAMP-stimulated
redistribution of a fraction of CLIC1 from a soluble to a membrane-associated form. We conclude that when expressed in Xenopus oocytes CFTR confers cAMP regulation to CLIC1 activity in the plasma membrane and that at least part of this regulation is
due to recruitment of CLIC1 from the cytoplasm to the membrane. |
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Keywords: | Chloride channel CLIC Cystic fibrosis transmembrane conductance regulator cAMP-activated chloride channel Cystic fibrosis NCC27 CLIC1 |
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