Downregulation of Epithelial Sodium Channel (ENaC) by CFTR Co-expressed in Xenopus Oocytes is Independent of Cl− Conductance

Downregulation of Epithelial Sodium Channel (ENaC) by CFTR Co-expressed in Xenopus Oocytes is... Defective regulatory interactions between the cystic fibrosis conductance regulator (CFTR) and the epithelial sodium channel (ENaC) have been implicated in the elevated Na+ transport rates across cystic fibrosis airway epithelium. It has recently been proposed that ENaC downregulation by CFTR depends on the ability of CFTR to conduct Cl− into the cell and is negligible when Cl− flows out of the cell. To study the mechanisms of this downregulation we have measured amiloride-inhibitable Na+ current (I amil ) in oocytes co-expressing rat ENaC and human wild-type CFTR. In oocytes voltage-clamped to −60 mV, stimulating CFTR with 1 mm IBMX reduced I amil by up to 80%, demonstrating that ENaC is inhibited when Cl− is conducted out of the cell. Decreasing the level of CFTR stimulation in a single oocyte, decreased both the degree of I amil downregulation and the CFTR-mediated plasma membrane Cl− conductance, suggesting a direct correlation. However, I amil downregulation was not affected when Cl− flux across oocyte membrane was minimized by holding the oocyte membrane potential near the Cl− reversal potential (67% ± 10% inhibition at −20 mV compared to 79% ± 4% at −60 mV) demonstrating that I amil downregulation was independent of the amount of current flow through CFTR. Studies with the Ca2+-sensitive photoprotein aequorin showed that Ca2+ is not involved in I amil downregulation by CFTR, although Ca2+ injection into the cytoplasm did inhibit I amil . These results demonstrate that downregulation of ENaC by CFTR depends on the degree of CFTR stimulation, but does not involve Ca2+ and is independent of the direction and magnitude of Cl− transport across the plasma membrane. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Downregulation of Epithelial Sodium Channel (ENaC) by CFTR Co-expressed in Xenopus Oocytes is Independent of Cl− Conductance

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 1999 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s002329900529
Publisher site
See Article on Publisher Site

Abstract

Defective regulatory interactions between the cystic fibrosis conductance regulator (CFTR) and the epithelial sodium channel (ENaC) have been implicated in the elevated Na+ transport rates across cystic fibrosis airway epithelium. It has recently been proposed that ENaC downregulation by CFTR depends on the ability of CFTR to conduct Cl− into the cell and is negligible when Cl− flows out of the cell. To study the mechanisms of this downregulation we have measured amiloride-inhibitable Na+ current (I amil ) in oocytes co-expressing rat ENaC and human wild-type CFTR. In oocytes voltage-clamped to −60 mV, stimulating CFTR with 1 mm IBMX reduced I amil by up to 80%, demonstrating that ENaC is inhibited when Cl− is conducted out of the cell. Decreasing the level of CFTR stimulation in a single oocyte, decreased both the degree of I amil downregulation and the CFTR-mediated plasma membrane Cl− conductance, suggesting a direct correlation. However, I amil downregulation was not affected when Cl− flux across oocyte membrane was minimized by holding the oocyte membrane potential near the Cl− reversal potential (67% ± 10% inhibition at −20 mV compared to 79% ± 4% at −60 mV) demonstrating that I amil downregulation was independent of the amount of current flow through CFTR. Studies with the Ca2+-sensitive photoprotein aequorin showed that Ca2+ is not involved in I amil downregulation by CFTR, although Ca2+ injection into the cytoplasm did inhibit I amil . These results demonstrate that downregulation of ENaC by CFTR depends on the degree of CFTR stimulation, but does not involve Ca2+ and is independent of the direction and magnitude of Cl− transport across the plasma membrane.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jun 1, 1999

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