Sodium channels epithelial

CFTR has a single-channel conductance of about 8 pS. It is present in the apical membranes of many epithelia. Its mutation leads to the potentially lethal disease cystic fibrosis. In addition to acting as a chloride channel, CFTR is also thought to regulate, e.g., the epithelial sodium channel ENaC, a molecularly unknown outwardly-rectifying chloride channel, and possibly also potassium channels and water channels. Some of these potential regulatory processes, however, are controversial. CFTR also acts as a receptor for bacteria. 

Rossier BC, Pradervand S, Schild L et al (2002) Epithelial sodium channel and the control of sodium balance interaction between genetic and environmental factors. Annu Rev Physiol 64 877-897... 

Kellenberger S, Schild L (2002) Epithelial sodium channel/degenerin family of ion channels a variety of functions for a shared structure. Physiol Rev 82 735-767... 

Disease-causing mutations are found in the cytoplasmic regulatory region of the (3 and y subunits of the epithelial sodium channel (ENaC) genes. In general, patients with Liddle s syndrome can be treated successfully with the ENaC inhibitor amiloride. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Benos, D. J. and Stanton, B. A. (1999). Functional domains within the degenerin/ epithelial sodium channel (Deg/ENaC) superfamily of ion channels, J. Physiol., 520, 631-644. 

Ion transport pathways across the luminal and basolateral membranes of collecting tubule and collecting duct cells. Inward diffusion of Na+ via the epithelial sodium channel (ENaC) leaves a lumen-negative potential, which drives reabsorption of and efflux of K+. (R, aldosterone receptor.)... 

Amiloride Blocks epithelial sodium channels in collecting tubules Reduces Na retention and wasting increases lithium clearance Hypokalemia from other diuretics reduces lithium-induced polyuria Orally active duration 24 h Toxicity Hyperkalemic metabolic acidosis... 

Corvol, P. (1995). Liddle s syndrome heritable human hypertension caused by mutations in the Beta subunit of the epithelial sodium channel. J. Endocrinol. Invest., 18(7), 592-594. 

Liddle s syndrome is an autosomal dominant form of hypertension. It is a disorder of the renal epithelial sodium channel, which has three subunits, a, j, and y, and mutations within the first two are associated with increased sodium channel activity [7, 36]. This causes excessive sodium absorption in the distal nephron of the kidney. It gives rise to hypoglycemia, low -renin, and low aldosterone. 

A form of salt loss in infancy was long considered to be due to renal tubules that were refractory to aldosterone. Recent studies have described variant roots of the condition, either mutations in the mineralocorticoid receptor, the genes coding the epithelial sodium channel (ENaC), or other causes [6]. Many infant patients recover spontaneously, probably due to maturation of proximal tubular function. 

Inoue T, Okauchi Y, Matsuzaki Y, Kuwajima K, Kondo H, Horiuchi N, Nakao K, Iwata M, Yokogoshi Y, Shintani Y, Bando H, Saito S (1998) Identification of a single cytosine base insertion mutation at Arg-597 of the / subunit of the human epithelial sodium channel in a family with Liddle s disease. Eur J Endocrinol 138 691 -697... 

Kizer N, Guo XL, Hruska K. 1997. Reconstitution of stretch-activated cation channels by expression of the alpha-subunit of the epithelial sodium channel cloned from osteoblasts. Proc Natl Acad Sci USA. 94 1013-8. 

Awayda et al. [278] suggested that CPZ-induced alteration of epithelial sodium channels (ENaC) could be a result of the influence exerted by the phe-niothiazine derivative on the membrane fluidity. To demonstrate it they used epithelial sodium channels expressed in Xenopus laevis oocytes as a model, and compared the effects of CPZ (9) and temperature on the ENaC activity. They have shown that a decrease of membrane order caused either by the increase of temperature or by incorporation of drug molecules into the membrane affected the conductance of epithelial sodium channels in a very... 

Subsequently, it was found that a motif in the S9-S10 part of the C-terminal is essential for CO activation [45], A similar behaviour has been observed for epithelial sodium channels [46], In the case of the human BKCa subunit, cysteine residues are important for channel sensitivity to CO [47],... 

Kanelis, V., Farrow, N.A., Kay, L. E., Rotin, D., and. Forman-Kay, J.D. (1998) NMR studies of tandem WW domains of Nedd4 in complex with a PY motif-containing region of the epithelial sodium channel,... 

Kretz O, Barbry P, Bock R, Lindemann B. Differential expression of RNA and protein of the three pore-forming subunits of the amiloride-sensitive epithelial sodium channel in taste buds of the rat. J. Histochem. Cytochem. 1999 47 51-64. 

Shigemura N, Islam AA, Sadamitsu C, Yoshida R, Yasumatsu K, Ninomiya Y. Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush. Chem. Senses 2005 30 531-538. 

Alpha epithelial sodium channel (aENaC) Collecting duct No effect on sodium and potassium balance [193]... 

Benos, D. J., Saccomani, G., and Sariban-Sohraby, S. (1987). The epithelial sodium channel. /. Biol Chem. 262,10613-10618. 

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