Feedback inhibition of rat amiloride-sensitive epithelial sodium channels expressed in Xenopus laevis oocytes
Article first published online: 8 SEP 2004
The Journal of Physiology
Volume 516, Issue 1, pages 31–43, April 1999
How to Cite
Abriel, H. and Horisberger, J.-D. (1999), Feedback inhibition of rat amiloride-sensitive epithelial sodium channels expressed in Xenopus laevis oocytes. The Journal of Physiology, 516: 31–43. doi: 10.1111/j.1469-7793.1999.031aa.x
- Issue published online: 8 SEP 2004
- Article first published online: 8 SEP 2004
- (Received 15 September 1998; accepted after revision 6 January 1999)
- 1Regulation of the amiloride-sensitive epithelial sodium channel (ENaC) is essential for the control of body sodium homeostasis. The downregulation of the activity of this Na+ channel that occurs when the intracellular Na+ concentration ([Na+]i) is increased is known as feedback inhibition. Although intracellular Na+ is the trigger for this phenomenon, its cellular and molecular mediators are unknown.
- 2We used the ‘cut-open oocyte’ technique to control the composition of the intracellular milieu of Xenopus oocytes expressing rat ENaCs to enable us to test several factors potentially involved in feedback inhibition.
- 3The effects of perfusion of the intracellular space were demonstrated by an electromicrographic study and the time course of the intracellular solution exchange was established by observing the effect of intracellular pH: a decrease from pH 7.4 to 6.5 reduced the amiloride-sensitive current by about 40 % within 2 min.
- 4Feedback inhibition was observed in non-perfused oocytes when Na+ entry induced a large increase in [Na+]i. Intracellular perfusion prevented feedback regulation even though the [Na+]i was allowed to increase to values above 50 mM.
- 5No effects on the amiloride-sensitive current were observed after changes in the concentration of Na+ (from 1 to 50 mM), Ca2+ (from 10 to 1000 nM) or ATP (from nominally free to 1 or 5 mM) in the intracellular perfusate.
- 6We conclude that feedback inhibition requires intracellular factors that can be removed by intracellular perfusion. Although a rise in [Na+]i may be the trigger for the feedback inhibition of the ENaC, this effect is not mediated by a direct effect of Na+, Ca2+ or ATP on the ENaC protein.