Funciones de los canales iónicos CFTR y ENAC en la fibrosis quística / CFTR and ENaC functions in cystic fibrosis

La fibrosis quística se debe a la ausencia o defecto del canal transmembrana regulador de la fibrosis quística (CFTR), un canal de cloruro codificado en el gen cftr que juega un papel clave en la homeostasis del agua e iones. El CFTR es activado por el AMPc y se localiza en las membranas apicales y basolaterales de las vías aéreas, intestino y glándulas exocrinas. Una de sus funciones primarias en los pulmones es mantener la capa de líquido superficial a través de su función de canal y regular el canal epitelial de sodio sensible al amiloride (ENaC). Se han identificado más de 1900 mutaciones en el gen cftr. La enfermedad se caracteriza por secreciones viscosas en las glándulas exocrinas y por niveles elevados de cloruro de sodio en el sudor. En la fibrosis quística el CFTR no funciona y el ENaC está desregulado; el resultado es un aumento en la reabsorción de sodio y agua con la formación de un líquido viscoso. En las glándulas sudoríparas tanto el Na+ como el Cl- se retienen en el lumen causando una pérdida de electrolitos durante la sudoración y el NaCl se elimina al sudor. Así, los niveles elevados de NaCl son la base del test del sudor inducido por pilocarpina, un método de diagnóstico para la enfermedad. En esta revisión se discuten los movimientos de Cl- y Na+ en las glándulas sudoríparas y pulmón así como el papel del ENaC en la patogénesis de la enfermedad.

Cystic fibrosis is caused by dysfunction or lack of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that has a key role in maintaining ion and water homoeostasis in different tissues. CFTR is a cyclic AMP-activated Cl- channel found in the apical and basal plasma membrane of airway, intestinal, and exocrine epithelial cells. One of CFTR’s primary roles in the lungs is to maintain homoeostasis of the airway surface liquid layer through its function as a chloride channel and its regulation of the epithelial sodium channel ENaC. More than 1900 CFTR mutations have been identified in the cftr gene. The disease is characterized by viscous secretions of the exocrine glands in multiple organs and elevated levels of sweat sodium chloride. In cystic fibrosis, salt and fluid absorption is prevented by the loss of CFTR and ENaC is not appropriately regulated, resulting in increased fluid and sodium resorption from the airways and formation of a contracted viscous surface liquid layer. In the sweat glands both Na+ and Cl- ions are retained in the lumen, causing significant loss of electrolytes during sweating. Thus, elevated sweat NaCl concentration is the basis of the classic pilocarpine-induced sweat test as a diagnostic feature of the disease. Here we discuss the ion movement of Cl- and Na+ ions in two tissues, sweat glands and in the air surface as well as the role of ENaC in the pathogenesis of cystic fibrosis.

Effection of lung fluid clearance disturbance in late preterm infants with respiratory distress syndrome / 国际儿科学杂志

In recent studies,it has been demonstrated that the clinical efficacy of surfactant is poor for late protein infants.Besides,this kind of infants have not infection or other risk factors that may lead to respiratory distress syndrome(RDS).Thus,it is speculated that the pathogenesis of RDS of late preterm infants is different from preterm infants.New researches show that,as the key point of Lung fluid transport via Epithelium,α-ENaC plays an important role in the pathogenesis of RDS of late preterm infants through the inhibition of lung fluid clearance and activity of surfactant.This review highlights the most important mechanisms of Lung fluid absorption barrier in RDS of late preterm infants.

Regulación por proteasas del canal de sodio sensible al amiloride (ENaC) / Amiloride sensitive sodium channels (ENaC) and their regulation by proteases

El ENaC es un canal que permite el movimiento de Na+ desde el líquido luminal hacia las células en numerosos epitelios reabsortivos y también en otros tejidos como la placenta. ENaC juega un papel crucial en la homeostasis de los electrolitos y volumen de líquido extracelular. Es regulado por numerosas hormonas, incluyendo la aldosterona y bloqueado por el diurético amiloride. El ENaC está formado por tres subunidades homólogas α, β y γ que forman el poro por el cual se mueven los iones Na+. Dos factores regulan la actividad del ENaC. 1) el número de canales insertos en la membrana celular y 2) la probabilidad de apertura o tiempo en que se encuentra abierto el canal. El número de canales es el resultado de un balance entre su síntesis y degradación. La probabilidad de apertura depende de la proteólisis de zonas específicas de las subunidades α y γ por múltiples proteasas dentro de la célula y en el espacio extracelular. Entre las proteasas más estudiadas se encuentran la furina, prostasina, elastasa, plasmina y tripsina. Existen sustancias endógenas que bloquean la actividad de estas proteasas como la aprotinina, la bikunina y la nexina-1 y la expresión de las proteasas y sus inhibidores es regulada a su vez por la aldosterona, la tasa de movimiento de Na y el TFGβ. En este trabajo presentamos algunos ejemplos de esta regulación y su potencial papel en condiciones normales y en ciertas enfermedades como la fibrosis quística, renales e hipertensión.

ENaC is a channel that mediates entry of Na+ from the luminal fluid into the cells in many reabsorbing epithelia and it is also expressed in human placenta. ENaC is crucial in the control of electrolyte and extracellular volume homeostasis. ENaC is regulated by several hormones, including aldosterone and blocked by amiloride and its analogs. ENaC channels are composed by three homologous subunits, α, β and γ that form the pore where Na ions are transported. Two factors regulate the activity of ENaC channels: 1) the number of channels inserted in the membrane and 2) the open probability of the channels or time that the channel is open. The number of channels is the result of a balance between the synthesis and degradation of ENaC channels. The open probability depends on the proteolysis of specific segments in the α and γ subunits of ENaC by multiple proteases inside of the cell or in the extracellular space. Among the most studied proteases are furin, prostasin, elastase, plasmin and trypsin. There are endogenous substances that block the activity of these proteases such as aprotinin, bikunin and nexin-1 and the expression of both, proteases and their inhibitors are controlled by the rate of Na+ movement, aldosterone and TFG-β levels. In this work we present some examples of this regulation and the potential role that this process may play under normal and pathological conditions such as cystic fibrosis, kidney diseases and hypertension.

Preeclampsia, migración celular y canales iónicos / Preeclampsia, cellular migration and ion channels

En la placenta humana, el sinciciotrofoblasto es la barrera que regula el transporte de nutrientes, solutos y agua entre la sangre materna y fetal. Dentro de este movimiento transepitelial se encuentra el del Na+, su contribución a la presión osmótica es fundamental en la regulación del volumen de líquido extracelular. El canal epitelial de sodio sensible al amiloride (ENaC) media el transporte de Na+ desde el lumen hacia el interior celular en numerosos epitelios absortivos. Está regulado por la aldosterona, vasopresina, catecolaminas, estrógenos y progesterona. Es bloqueado por el amiloride y sus análogos. Para su activación, diversas proteasas lo escinden en la membrana plasmática y esto a su vez es regulado por la aldosterona. El ENaC está expresado también en la placenta humana y aunque su función no es conocida, podría participar en la homeostasis de agua y electrolitos. El ENaC también es influenciado por el estado de las proteínas del citoesqueleto y los cambios en el volumen celular alteran a su vez a éste. De esta manera existe una relación entre el ENaC y el citoesqueleto. Además, las corrientes de Na+ por el ENaC y otros canales de sodio participan en la migración celular en células normales y cancerosas. Aquí presentamos evidencias que avalan la hipótesis que el ENaC es necesario para la migración celular en células BeWo, derivadas del trofoblasto humano, que sintetizan hormonas y expresan el ENaC. Las células BeWO han sido utilizadas como modelo experimental para estudiar el transporte en células de placenta.

The syncytiotrophoblast acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. This transepithelial transport involves movement of Na+ and its contribution to the osmotic pressure is an important determinant of the extracellular fluid volume. ENaC is a channel that mediates entry of Na+ from the luminal fluid into the cells in many reabsorbing epithelia; it is aldosterone, vasopressin, insulin and catecholamine-inducible, modulated by estrogens and progesterone and blocked by amiloride and its analogs. Multiple proteases are involved in the proteolytic processing and activation of ENaC subunits and aldosterone alters the protease-protease inhibitors balance. ENaC is also expressed in human placenta; although its function is not well known, the Na+ conductive properties may participate in electrolyte and extracellular volume homeostasis. The activity of ENaC channels and other ion channels and transporters is regulated by the state of actin filaments; on the other hand, changes in volume influence the actin cytoskeleton. Thus, there is an interaction between ENaC and components of the apical membrane cytoskeleton. In addition to their role in cellular homeostasis and electrical properties, Na+ currents through ENaC and other sodium channels are involved in cell migration, well documented in normal and cancer cells. In this work we presented evidences supporting the hypothesis that ENaC channels are required for the migration of BeWo cells, a human hormone-synthesizing trophoblastic cell line that express the three subunits of the ENaC channels. BeWo cell line has also been used as a model to investigate the placental transport mechanisms.

Effect of iipopclysaccharide on ENaC expression in the lung of rats with acute lung injured / 中华急诊医学杂志

Objective To study the effect of lipopolysaccharide(LPS)on the endo-pulmonary natrium channel(ENaC)expression in the lung of rats with acute lung injured.Method Sixteen rats were randomly divided into normal control group and LPS-group.Rats of normal control group and LPS-group were killed at 6 hours after intravenous injection of normal saline(8 ml/kg)or LPS(8 mg/kg).The extent of lung injury was assessed by arterial blood gas analysis and histological examination.At the same time,?-ENaC protein and???- ENaC mRNA expression in the lung tissue were analyzed by immunohistochemistry and RT-PCR.Results PaO_2 in LPS-group was noticeably lower than in normal control group(P

Study on Expression of ENaC and rBSCl of Kidney Tissue in Lung-Qi Deficiency Model Rats / 中国中医药信息杂志

Objective To study the relationship of lung and kidney in TCM by detecting the protein expression related to Na+ transportation in the kidney tissue of Lung-Qi deficiency model rats.Methods Lung-Qi deficiency model of rats were copied.Immunohistochemistry was applied to measure the expressions of ENaC and rBSCl in renal tubular epithelium.RIA was used to detect ALD and ANP levels in plasma and lung tissue.Results Compared with the control group,expressions of ENaC and rBSCl of renal tubule were upregulated markedly,ALD level increased and ANP level decreased obviously in the model group.Conclusion Lung can regulate the expressions of ENaC and rBSCl in the renal tubule by secreting ALD and ANP,which can regulate Na+ and water reabsorption in the renal tubule and then influence the water metabolism of the body.

Clinical study on postoperative analgesia following sinonasal surgery / 中国耳鼻咽喉头颈外科

0.05), though scores of both group were significantly lower than that of group T(P

Altered expression of sodium transporters in the excretory duct-ligated submandibular gland in rat

Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney / 대한신장학회잡지

BACKGROUND: Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days. RESULTS: Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. CONCLUSION: These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.

A Case of Liddle's Syndrome in a Seventy One-year Old Woman / 대한신장학회잡지

Liddle's syndrome is a rare inherited disease with characteristic clinical manifestations of hypertension and hypokalemic metabolic alkalosis. Markedly suppressed serum aldosterone and renin levels are important laboratory findings to differentiate this disorder from primary hyperaldosteronism. When Liddle et al. reported the disorder in 1963, they proposed aggressive Na+ absorption and increased excretion of K+ as the pathogenesis of the syndrome. Since then, specific mutation in the epithelial Na+ channel located in the collecting duct of the kidney has been elucidated as a disease mechanism. Liddle's syndrome is inherited by an autosomal dominant trait and generally the onset of the syndrome is before the age of 20 with increased risk of premature death due to stroke or heart failure. Recently, however, a few cases of late onset and genetically proven nonfamilial cases with de novo mutation of beta or gamma Na+ channel have been reported. We report a case of seventy-one year old woman who had hypertension with hypokalemic metabolic alkalosis and was diagnosed as Liddle's syndrome. Further evaluation revealed low serum renin and aldosterone levels. Primary aldosteronism, Cushing's syndrome, glucocorticoid remediable aldosteronism and deficiency of 11beta-OHase and 17alpha-OHase were ruled out based on her laboratory data and history. Her hypertension and hypokalemia responded to amiloride treatment but not to spironolactone.

Contributory Roles of Distal Renal Sodium Transporters in NSAID-induced Sodium Retention / 대한신장학회잡지

BACKGROUND: Sodium retention occurs in some patients taking NSAIDs (nonsteroidal anti-inflammatory drugs). Although the renal effects of NSAIDs are predominantly mediated through the inhibition of prostaglandins synthesized by cyclooxygenase-2 (COX-2), the mechanisms of sodium retention are not clear at the sodium transporter levels in the kidney. Previous studies have shown that compensatory upregulation of COX-2 is induced in renal medulla by high salt intake and that NSAID-induced sodium retention may be transitory. METHODS: To investigate whether renal sodium transporter abundances are altered by NSAID administration and whether renal sodium transporter abundances are affected by high salt intake or chronic NSAID administration, we performed an acute study treated with a single injection of diclofenac and another chronic study treated with 7 days' administration of DFU, a selective COX-2 inhibitor, using semiquantitative immunobotting from rat kidneys. Male Sprague-Dawley rats were divided into three groups in each study: controls, NSAID treatment, and high-salt intake plus NSAID treatment. The control diet contained sodium 1 mmol/200 g BW/day, and the high-salt diet 10 mmol/200 g BW/day. RESULTS: The acute study using diclofenac (100 mg/kg BW) increased the abundances of NKCC2 (by 73%) and ENaC-alpha (by 60%) in cortex and of NKCC2 (by 165%) and ENaC-alpha (by 91%) in outer medulla, in association with a significant decrease in urinary sodium excretion. The increased ENaC-alpha abundance was reversed by addition of high salt intake in both cortex and outer medulla. The chronic study using DFU (40 mg/kg/d for 7 days) showed no significant changes in distal renal sodium transporters except a decreased abundance of Na-K- ATPase alpha1-subunit (by 24%) in outer medulla. The addition of high salt intake decreased the abundances of ENaC-alpha (by 35%) and ENaC-beta (by 47 %) in outer medulla. CONCLUSION: The abundances of thick ascending limb NKCC2 and collecting duct ENaC are altered in response to NSAID administration. It is suggested that NKCC2 & ENaC are contributory to NSAID- induced sodium retention and also have a compensatory role in high salt intake and chronic NSAID administration.

Control of Na+ channels in salivary duct cells

No abstract available.

Regulation of Na+ absorption and Cl- secretion in the endometrium: switching mechanisms

No abstract available.

Unexpected effects of pathogens on epithelial Na+ channels

No abstract available.