| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MOLECULAR AND GENOMIC |
1 Department of Physiology and Biophysics
2 Graduate Program in Neuroscience
3 Graduate Program in Physiology, Biophysics and Systems Biology, Weill Medical College of Cornell University, New York, NY 10021, USA
The regulation of epithelial Na+ channel (ENaC) activity by Na+ was studied in Xenopus oocytes using two-electrode voltage clamp and patch-clamp recording techniques. Here we show that amiloride-sensitive Na+ current (INa) is downregulated when ENaC-expressing cells are exposed to high extracellular [Na+]. The reduction in macroscopic Na+ current is accompanied by an increase in the concentration of intracellular Na+ ([Na+]i) and is only slowly reversible. At the single-channel level, incubating oocytes in high-Na+ solution reduces open probability (Po) approximately twofold compared to when [Na+] is kept low, by increasing mean channel closed times. However, increasing Po by introducing a mutation in the ß-subunit (S518C) which, in the presence of [2-(trimethylammonium) ethyl] methane thiosulfonate (MTSET), locks the channel in an open state, could not alone abolish the downregulation of macroscopic current measured with exposure to high external [Na+]. Inhibition of the insertion of new channels into the plasma membrane using Brefeldin A revealed that surface channel lifetime is also markedly reduced under these conditions. In channels harbouring a ß-subunit mutation, R564X, associated with Liddle's syndrome, open probability in both high- and low-Na+ conditions is significantly higher than in wild-type channels. Increasing the Po of these channels with an activating mutation abrogated the difference in macroscopic current observed between groups of oocytes incubated in high- and low-Na+ conditions. These findings demonstrate that reduction of ENaC Po is a physiological mechanism limiting Na+ entry when [Na+]i is high.
(Received 7 March 2006;
accepted after revision 5 May 2006;
first published online 11 May 2006)
Corresponding author L. G. Palmer: Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. Email: lgpalm{at}med.cornell.edu
This article has been cited by other articles:
|
|
 |
|
  K. K. Knight, D. M. Wentzlaff, and P. M. Snyder Intracellular Sodium Regulates Proteolytic Activation of the Epithelial Sodium Channel J. Biol. Chem., October 10, 2008; 283(41): 27477 - 27482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Frindt, Z. Ergonul, and L. G. Palmer Surface Expression of Epithelial Na Channel Protein in Rat Kidney J. Gen. Physiol., June 1, 2008; 131(6): 617 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bertog, J. E. Cuffe, S. Pradervand, E. Hummler, A. Hartner, M. Porst, K. F. Hilgers, B. C. Rossier, and C. Korbmacher Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome J. Physiol., January 15, 2008; 586(2): 459 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Oberleithner, C. Riethmuller, H. Schillers, G. A. MacGregor, H. E. de Wardener, and M. Hausberg Plasma sodium stiffens vascular endothelium and reduces nitric oxide release PNAS, October 9, 2007; 104(41): 16281 - 16286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Althaus, R. Bogdan, W. G. Clauss, and M. Fronius Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability FASEB J, August 1, 2007; 21(10): 2389 - 2399. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
