scholarly journals The epithelial sodium channel in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi)

2012 ◽  
Vol 279 (1748) ◽  
pp. 4795-4802 ◽  
Author(s):  
Minoru Uchiyama ◽  
Sho Maejima ◽  
Sumio Yoshie ◽  
Yoshihiro Kubo ◽  
Norifumi Konno ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Transport ◽  
Sodium Current ◽  
Apical Cell ◽  
Epithelial Sodium Channel ◽  
Sodium Absorption ◽  
Apical Cell Membrane ◽  
Rate Limiting ◽  
Complementary Rnas ◽  
Australian Lungfish

Epithelial sodium channel (ENaC) is a Na + -selective, aldosterone-stimulated ion channel involved in sodium transport homeostasis. ENaC is rate-limiting for Na + absorption in the epithelia of osmoregulatory organs of tetrapods. Although the ENaC/degenerin gene family is proposed to be present in metazoans, no orthologues or paralogues for ENaC have been found in the genome databases of teleosts. We studied full-length cDNA cloning and tissue distributions of ENaCα, β and γ subunits in the Australian lungfish, Neoceratodus forsteri , which is the closest living relative of tetrapods. Neoceratodus ENaC ( n ENaC) comprised three subunits: n ENaCα, β and γ proteins. The n ENaCα, β and γ subunits are closely related to amphibian ENaCα, β and γ subunits, respectively. Three ENaC subunit mRNAs were highly expressed in the gills, kidney and rectum. Amiloride-sensitive sodium current was recorded from Xenopus oocytes injected with the n ENaCαβγ subunit complementary RNAs under a two-electrode voltage clamp. n ENaCα immunoreactivity was observed in the apical cell membrane of the gills, kidney and rectum. Thus, n ENaC may play a role in regulating sodium transport of the lungfish, which has a renin–angiotensin–aldosterone system. This is interesting because there may have been an ENaC sodium absorption system controlled by aldosterone before the conquest of land by vertebrates.

Epithelial sodium channel in human epidermal keratinocytes: expression of its subunits and relation to sodium transport and differentiation

1999 ◽  
Vol 112 (19) ◽  
pp. 3343-3352 ◽  
Author(s):  
M. Brouard ◽  
M. Casado ◽  
S. Djelidi ◽  
Y. Barrandon ◽  
N. Farman
Keyword(s):  
Sodium Channel ◽  
Sodium Transport ◽  
Human Keratinocytes ◽  
Epithelial Sodium Channel ◽  
Epidermal Keratinocytes ◽  
Sodium Absorption ◽  
Human Epidermal Keratinocytes ◽  
Keratinocyte Proliferation ◽  
Protein Levels ◽  
Cultured Keratinocytes

The amiloride-sensitive epithelial sodium channel (ENaC) is a main determinant of sodium absorption in renal and colonic epithelial cells. Surprisingly, it is also expressed in non-transporting epithelia such as the epidermis. To gain insight into the putative role of ENaC in keratinocytes, we have evaluated its expression in human skin and in cultured human keratinocytes. Our results indicate that (1) ENaC is expressed in the epidermis and in cultured keratinocytes, at the mRNA and at the protein levels, (2) the ratio of expression of the different ENaC subunits is drastically modified at the protein level during cell growth and differentiation, with a selective upregulation of the β subunit, (3) no transepithelial sodium transport function is apparent in cultured keratinocytes, but patch-clamp recordings indicate the existence of functional sodium channels with properties similar to those of the cloned ENaC and (4) ENaC inhibition does not alter keratinocyte proliferation, but it significantly decreases the frequency of dome formation in confluent keratinocyte cultures. These results document for the first time the characteristics of ENaC subunit expression in human keratinocytes, and suggest that ENaC may be important during differentiation.

Ca2(+)-dependent inhibition of sodium transport in rabbit cortical collecting tubules

1990 ◽  
Vol 258 (3) ◽  
pp. F568-F582 ◽  
Author(s):  
G. Frindt ◽  
E. E. Windhager
Keyword(s):  
Cell Membrane ◽  
Amphotericin B ◽  
Apical Cell ◽  
Ringer Solution ◽  
Na Transport ◽  
Apical Cell Membrane ◽  
Dependent Inhibition ◽  
Collecting Tubules ◽  
Rate Limiting ◽  
Sustained Increase

Experiments were carried out to test whether maneuvers believed to increase intracellular Ca2+ concentration [( Ca2+]cell) inhibit Na transport in cortical collecting tubules (CCTs). Unidirectional Na efflux (JNa1----b) and Na influx (JNab----1) were measured isotopically in isolated perfused renal CCTs of rabbits. The animals were either untreated or pretreated with deoxycorticosterone (DOC) for 1-3 wk. To raise [Ca2+]cell, ionomycin or quinidine were added to, or [Na] reduced in, pertubular fluid. In control DOC-pretreated CCTs JNa1----b tended to saturate as luminal Na concentration was increased, reaching 22.9 +/- 1.2 pmol.cm-1.s-1 at 145 mM. In addition, in these CCTs, in contrast to non-DOC-treated tubules, the apical cell membrane was not found to be rate limiting for Na reabsorption as neither amphotericin B nor vasopressin further enhanced JNa1----b. In non-DOC-treated CCTs 10(-6) M ionomycin inhibited JNa1----b by 44.7%. When DOC-pretreated CCTs were exposed to either 10(-6)M ionomycin or 10(-4)M quinidine, JNa1----b was inhibited by 27 and 26%, respectively, while JNab----1 remained unchanged. This ionomycin-induced inhibition was Ca dependent. Exposure of DOC-pretreated CCTs to 5 mM Na-Ringer solution (Na replaced by choline or N-methyl-D-glucamine) for 30 min reduced JNa1----b by 18-30%. The inhibition of JNa1----b caused by any of the three maneuvers was fully reversed upon addition of amphotericin B to the luminal fluid. The results are consistent with the view that a sustained increase in [Ca2+]cell reduces Na transport by inhibition of the rate of Na+ entry across the apical cell membrane.

Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport

2011 ◽  
Vol 43 (13) ◽  
pp. 844-854 ◽  
Author(s):  
Romain A. Studer ◽  
Emilie Person ◽  
Marc Robinson-Rechavi ◽  
Bernard C. Rossier
Keyword(s):  
Sodium Channel ◽  
Sodium Transport ◽  
Salt Intake ◽  
Epithelial Sodium Channel ◽  
Cell Junctions ◽  
Limiting Factors ◽  
Last Common Ancestor ◽  
Β Subunit ◽  
Α Subunit ◽  
Additional Function

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi , an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment (“internal milieu”) precedes the emergence of other key elements of the aldosterone signaling pathway.

The collecting tubule of Amphiuma. II. Effects of potassium adaptation

1987 ◽  
Vol 253 (6) ◽  
pp. F1273-F1282 ◽  
Author(s):  
J. D. Horisberger ◽  
M. Hunter ◽  
B. Stanton ◽  
G. Giebisch
Keyword(s):  
Sodium Current ◽  
Apical Cell ◽  
Potassium Conductance ◽  
Transport Pathway ◽  
High Potassium ◽  
Apical Cell Membrane ◽  
High Sodium ◽  
Collecting Tubule ◽  
Potassium Secretion ◽  
Collecting Tubules

Electrophysiological and transport properties were studied in isolated and perfused Amphiuma collecting tubules from two groups of animals, one exposed to a high sodium (NA), the other to a high potassium (KA) environment (both conditions known to modulate blood aldosterone levels). The transepithelial lumen-negative potential was significantly larger (-38 +/- 5 mV) in tubules from KA animals than from NA animals (-15 +/- 3 mV). In addition, we observed an increase in the apical amiloride-sensitive sodium conductance and stimulation of the transepithelial sodium current. Although no measurable potassium conductance was found in the apical cell membrane in either group, a potassium selectivity of the paracellular transport pathway was observed in the KA animals. Net potassium secretion was demonstrated in KA tubules (helium-glow photometry and [3H]inulin analysis). Potassium secretion was abolished by luminal amiloride but imposition of a bath-to-lumen potassium gradient induced potassium secretion. We conclude that in contrast to the mammalian cortical collecting tubule in which potassium secretion is largely transcellular, potassium secretion in the Amphiuma collecting tubule is by diffusion through the paracellular pathway.

Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney

2000 ◽  
Vol 279 (1) ◽  
pp. F46-F53 ◽  
Author(s):  
Carolyn A. Ecelbarger ◽  
Gheun-Ho Kim ◽  
James Terris ◽  
Shyama Masilamani ◽  
Carter Mitchell ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Transport ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Acute Administration ◽  
Brattleboro Rats ◽  
Water Restriction ◽  
Short Term

Sodium transport is increased by vasopressin in the cortical collecting ducts of rats and rabbits. Here we investigate, by quantitative immunoblotting, the effects of vasopressin on abundances of the epithelial sodium channel (ENaC) subunits (α, β, and γ) in rat kidney. Seven-day infusion of 1-deamino-[8-d-arginine]-vasopressin (dDAVP) to Brattleboro rats markedly increased whole kidney abundances of β- and γ-ENaC (to 238% and 288% of vehicle, respectively), whereas α-ENaC was more modestly, yet significantly, increased (to 142% of vehicle). Similarly, 7-day water restriction in Sprague-Dawley rats resulted in significantly increased abundances of β- and γ- but no significant change in α-ENaC. Acute administration of dDAVP (2 nmol) to Brattleboro rats resulted in modest, but significant, increases in abundance for all ENaC subunits, within 1 h. In conclusion, all three subunits of ENaC are upregulated by vasopressin with temporal and regional differences. These changes are too slow to play a major role in the short-term action of vasopressin to stimulate sodium reabsorption in the collecting duct. Long-term increases in ENaC abundance should add to the short-term regulatory mechanisms (undefined in this study) to enhance sodium transport in the renal collecting duct.

scholarly journals Epithelial Sodium Channel-Mediated Sodium Transport Is Not Dependent on the Membrane-Bound Serine Protease CAP2/Tmprss4

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135224 ◽  
Author(s):  
Anna Keppner ◽  
Ditte Andreasen ◽  
Anne-Marie Mérillat ◽  
Julie Bapst ◽  
Camille Ansermet ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Serine Protease ◽  
Sodium Transport ◽  
Epithelial Sodium Channel ◽  
Membrane Bound

scholarly journals A Family with Liddle’s Syndrome Caused by a New Missense Mutation in the β Subunit of the Epithelial Sodium Channel

1998 ◽  
Vol 83 (6) ◽  
pp. 2210-2213 ◽  
Author(s):  
Junnosuke Inoue ◽  
Taisuke Iwaoka ◽  
Hiroshi Tokunaga ◽  
Kazufumi Takamune ◽  
Shojiro Naomi ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Missense Mutation ◽  
Sodium Current ◽  
Epithelial Sodium Channel ◽  
Missense Mutations ◽  
Β Subunit ◽  
Dominant Form ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Py Motif

Liddle’s syndrome is an autosomal dominant form of salt sensitive hypertension caused by mutations in the β or γ subunit of the epithelial sodium channel. Systemic mutagenesis studies revealed that a conserved PPPXY sequence (PY motif) of the C-terminus of the α, β, or γ subunits might be involved in the regulation of the channel activity. However, only two missense mutations in the PY motif of theβ subunit have been reported to cause Liddle’s syndrome. We sequenced the C-termini of the β and γ subunits of the epithelial sodium channel in a Japanese family clinically diagnosed as having Liddle’s syndrome and found a new missense mutation in the PY motif of the β subunit, P615S. Expression studies with P615S mutant in Xenopus oocytes resulted in an about 3-fold increase in the amiloride-sensitive sodium current compared to the wild type (p = 0.001). These findings provide further clinical evidence for the hypothesis that a conserved PY motif may be critically important for the regulation of the epithelial sodium channel.

scholarly journals Regulation of the epithelial sodium channel by accessory proteins

2003 ◽  
Vol 371 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Kelly GORMLEY ◽  
Yanbin DONG ◽  
Giuseppe A. SAGNELLA
Keyword(s):  
Blood Pressure ◽  
Cystic Fibrosis ◽  
Sodium Channel ◽  
Sodium Transport ◽  
Genetic Disorders ◽  
Epithelial Sodium Channel ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Channel Activity ◽  
Cellular Mechanisms

The epithelial sodium channel (ENaC) is of fundamental importance in the control of sodium fluxes in epithelial cells. Modulation of sodium reabsorption through the distal nephron ENaC is an important component in the overall control of sodium balance, blood volume and thereby of blood pressure. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohypoaldosteronism type 1), associated with contrasting effects on blood pressure. The mineralocorticoid aldosterone is a well-established modulator of sodium-channel activity. Considerable insight has now been gained into the intracellular signalling pathways linking aldosterone-mediated changes in gene transcription with changes in ion transport. Activating pathways include aldosterone-induced proteins and especially the serum- and glucocorticoid-inducible kinase (SGK) and the small G-protein, K-Ras 2A. Targeting of the ENaC for endocytosis and degradation is now emerging as a major mechanism for the down-regulation of channel activity. Several proteins acting in concert are an intrinsic part of this process but Nedd4 (neural precursor cell expressed developmentally down-regulated 4) is of central importance. Other mechanisms known to interact with ENaC and affect sodium transport include channel-activating protease 1 (CAP-1), a membrane-anchored protein, and the cystic fibrosis transmembrane regulator. The implications of research on accessory factors controlling ENaC activity are wide-ranging. Understanding cellular mechanisms controlling ENaC activity may provide a more detailed insight not only of ion-channel abnormalities in cystic fibrosis but also of the link between abnormal renal sodium transport and essential hypertension.

Cellular organization of urinary acidification

1986 ◽  
Vol 251 (2) ◽  
pp. F173-F187 ◽  
Author(s):  
P. R. Steinmetz
Keyword(s):  
Apical Membrane ◽  
Apical Cell ◽  
Freeze Fracture ◽  
Transport Systems ◽  
Sodium Absorption ◽  
Bicarbonate Secretion ◽  
Transport Pathway ◽  
Apical Cell Membrane ◽  
Membrane Area ◽  
Urinary Acidification

The turtle bladder contains transport systems for active sodium absorption, electrogenic proton secretion, and bicarbonate secretion (coupled to chloride absorption) that are functionally separate and occur in specialized epithelial cells. Maneuvers that alter the intracellular acid-base state, such as changes in PCO2, cause marked changes in the apical membrane area of alpha-type carbonic anhydrase (CA) cells by addition or retrieval of membrane vesicles but have no effect on the granular cells that transport sodium. The apical cell membrane of alpha-CA cells contains characteristic rod-shaped intramembrane particles (RSP) by freeze fracture and is coated on its cytoplasmic side with studs. A subpopulation of CA cells (beta-type), which is characterized by apical microvilli, fails to exhibit an apical response to CO2 stimulation and does not reveal RSPs or studs at its apical membranes; instead, these elements can be demonstrated at the basolateral membrane. The reversal in the polarity of these elements as well as physiological evidence suggest that beta-type cells are responsible for bicarbonate secretion. Structure-function studies of CO2 stimulation of H+ secretion by alpha-CA cells indicate that the secretion rate (JH) correlates with apical membrane area and numbers of RSPs. The view that RSPs represent arrays of transmembrane channels and that studs represent catalytic units of H+ pumps is supported by quantitative considerations but remains to be proven. Urinary acidification is regulated not only by changes in the number of H+ pumps but also by the intrinsic properties of the H+ pump itself. For a given pump population, JH is closely controlled by the delta microH across the active transport pathway.

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