Epithelial Na+ channels

Prototypic inhibitor of the family of Na/H exchangers and of epithelial Na+ channels. 

Epithelial Na Channel. Figure 1 Transepithelial ion transport in a principal cell of the aldosterone-sensitive distal nephron (ASDN). 

Palmer LG, Garty H (2000) Epithelial Na Channels. In Seldin DW, Giebisch G, (eds.) The Kidney physiology and pathophysiology, 3rdedn, vol 1. Lippincot Williams Wilkins Philadelphia, pp 251—276... 

Renin-Angiotensin-Aldosterone System Epithelial Na+ Channels ACE Inhibitors... 

Liddle s syndrome is an autosomal dominant disorder that is caused by persistent hyperactivity of the epithelial Na channel. Its symptoms mimic aldosterone excess, but plasma aldosterone levels are actually reduced (pseudoaldosteronism). The disease is characterized by early onset arterial hypertension, hypokalemia, and metabolic alkalosis. 

C. Ruckes, U. Blank, K. Moller, J. Rieboldt, H. Lindemann, G. Munker, W. Clauss, and W. M. Weber. Amiloride-sensitive Na+ channels in human nasal epithelium are different from classical epithelial Na+ channels. Biochem Biophys Res Commun 237 488-491 (1997). 

Shlyonsky V, Goolaerts A, van Beneden R, Sariban-Sohraby S (2005) Differentiation of epithelial Na + channel function. An in vitro model. J Biol Chem 280(25) 24181-24187... 

Staub, O., S. Dho, P. Henry, J. Correa, T. Ishikawa, J. McGlade, and D. Rotin. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle s syndrome. Embo J. 15 2371-80.1996. 

Staub, O., I. Gautschi, T. Ishikawa, K. Breitschopf, A. Ciechanover, L. Schild, and D. Rotin. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. Embo J. 16 6325-36.1997. 

Both agents appear to affect Na+ reabsorption in the cortical collecting duct. A site in the connecting tubule also may be involved. Although amiloride has been more extensively studied than triamterene, both diuretics specifically block the apical membrane epithelial Na channel (ENaC) (Fig. 21-5).The reduced rate of Na+ reabsorption diminishes the gradient that facih-tates K+ secretion. K+ secretion by the collecting duct principal cells is a passive phenomenon that depends on and is secondary to the active reabsorption of Na+. 

Reabsorption of Na+ via the epithelial Na channel (ENaC) and its coupled secretion of K+ is regulated by aldosterone. This steroid hormone, through its actions on gene transcription, increases the activity of both apical membrane channels and the basolateral Na+/K+ ATPase. This leads to an increase in the transepithelial electrical potential and a dramatic increase in both Na+ reabsorption and K+ secretion. 

Spironolactone and eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. Amiloride and triamterene do not block aldosterone, but instead directly interfere with Na+ entry through the epithelial Na+ channels (ENaC) in the apical membrane of the collecting tubule. Since K+ secretion is coupled with Na+ entry in this segment, these agents are also effective potassium-sparing diuretics. 

Impairs alveolar fluid clearance by inhibiting epithelial Na channels [178]... 

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