Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits

Canessa, Cecilia M.; Schild, Laurent; Buell, Gary; Thorens, Bernard; Gautschi, Ivan; Horisberger, Jean‐Daniel; Rossier, Bernard C.

doi:10.1038/367463a0

Cited by 1,850 publications

(1,537 citation statements)

References 30 publications

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“…Amiloride, a diuretic agent known to block Na + /H + , Na + /Ca 2+ exchangers and ENaC [40,41], is a non-specific blocker for ASICs. It reversibly inhibits the ASIC currents with an IC 50 of 10 -50 μM [10,13,24,28,42].…”

Section: Pharmacological Characterization Of Asics Amiloridementioning

confidence: 99%

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Xiong

Pignataro²,

et al. 2008

Current Opinion in Pharmacology

212

161

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A significant drop of tissue pH or acidosis is a common feature of acute neurological conditions such as ischemic stroke, brain trauma, and epileptic seizures. Acid-sensing ion channels, or ASICs, are proton-gated cation channels widely expressed in peripheral sensory neurons and in the neurons of the central nervous system. Recent studies have demonstrated that activation of these channels by protons plays an important role in a variety of physiological and pathological processes such as nociception, mechanosensation, synaptic plasticity, and acidosis-mediated neuronal injury. This review provides an overview of the recent advance in electrophysiological, pharmacological characterization of ASICs, and their role in neurological diseases. Therapeutic potential of current available ASIC inhibitors is discussed.

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Section: Pharmacological Characterization Of Asics Amiloridementioning

confidence: 99%

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Xiong

Pignataro²,

et al. 2008

Current Opinion in Pharmacology

212

161

View full text Add to dashboard Cite

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“…The cloning of the amiloride-sensitive EnaC (Canessa et al, 1993), which is made of three homologous subunits (Canessa et al, 1994), enabled subsequent genetic experiments supporting a central role for the so-called alpha subunit of this channel in the clearance of fetal lung liquid at birth.…”

Section: Markers Of Hydration Status and Complex Conditions Of The Lumentioning

confidence: 99%

Mild dehydration: a risk factor of broncho-pulmonary disorders?

Kalhoff¹

2003

Eur J Clin Nutr

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Several expert committees recommend a high fluid intake in patients with chronic bronchitis and asthma. Is there a relationship between fluid intake or hydration status and broncho-pulmonary disorders like bronchitis and asthma? First, basic physiologic mechanisms like regulation of lung fluid balance and water transport at pulmonary surfaces were analyzed, in order to characterize the role of local hydration status in lung and airways. Second, making use of the computerbased literature searches (PubMed), evidence for a role of hydration status in complex physiological and pathophysiological conditions of lungs and airways like perinatal lung adaptation (PLA) (in prematures), mucociliary clearance(MC) and asthma was categorized. The movement of fluid between the airspaces, interstitium, and vascular compartments in the lungs plays an important physiological role in the maintenance of hydration and protection of the lung epithelium and significantly contributes to a proper airway clearance. PLA is characterized by a rapid change from fluid secretion to fluid absorption in the distal respiratory tract, with the literature data confirming a critical role of the epithelial sodium channel. Only few studies have investigated the effect of different fluid input regimens on PLA in prematures. MC relies on the interaction between epithelial water fluxes, mucus secretions, and ciliary activity. Whereas animal data show that drying of the airway epithelium decreases MC, few clinical studies investigating the effect of local or systemic hydration on MC have led to ambiguous results. Asthma (A) is characterized by chronic airway inflammation and episodic airway obstruction. Data in animals and humans indicate an association between exercise-induced-A and conditioning (humidity and heat exchange) of inspired air. However, epidemiological studies (children and adults), investigating the role of fluid (and salt) input in the etiology of the disease as well as studies analyzing different markers of hydration status during asthmatic attacks have so far led to conflicting results. Some expert groups recommend sufficient hydration as a complementary A-therapy. Analysis of basic physiological mechanisms in lungs and airways clearly demonstrates a critical role for water transport and local hydration status. In broncho-pulmonary diseases, however, analysis of the complex pathophysiological mechanisms is difficult. Thus, we still need more studies to confirm or refute mild dehydration or hypohydration as a risk factor of broncho-pulmonary disorders.

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“…Because of the availability of rENaC (26), this study was undertaken to test the hypothesis that short actin filaments could modulate the activity of rENaC and that PKA sensitivity could be conferred onto rENaC, but only in the presence of actin. For this study, we used a reconstitution system in which a single ␣,␤,␥-rENaC could be examined (27).…”

mentioning

confidence: 99%

Regulation of Epithelial Sodium Channels by Short Actin Filaments

Berdiev

Prat

Cantiello

et al. 1996

Journal of Biological Chemistry

149

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Cytoskeletal elements play an important role in the regulation of ion transport in epithelia. We have studied the effects of actin filaments of different length on the ␣, ␤, ␥-rENaC (rat epithelial Na ؉ channel) in planar lipid bilayers. We found the following. 1) Short actin filaments caused a 2-fold decrease in unitary conductance and a 2-fold increase in open probability (P o ) of ␣,␤,␥-rENaC. 2) ␣,␤,␥-rENaC could be transiently activated by protein kinase A (PKA) plus ATP in the presence, but not in the absence, of actin. 3) ATP in the presence of actin was also able to induce a transitory activation of ␣,␤,␥-rENaC, although with a shortened time course and with a lower magnitude of change in P o . 4) DNase I, an agent known to prohibit elongation of actin filaments, prevented activation of ␣,␤,␥-rENaC by ATP or PKA plus ATP. 5) Cytochalasin D, added after rundown of ␣,␤,␥-rENaC activity following ATP or PKA plus ATP treatment, produced a second transient activation of ␣,␤,␥-rENaC. 6) Gelsolin, a protein that stabilizes polymerization of actin filaments at certain lengths, evoked a sustained activation of ␣,␤,␥-rENaC at actin/gelsolin ratios of <32:1, with a maximal effect at an actin/gelsolin ratio of 2:1. These results suggest that short actin filaments activate ␣,␤,␥-rENaC. PKA-mediated phosphorylation augments activation of this channel by decreasing the rate of elongation of actin filaments. These results are consistent with the hypothesis that cloned ␣,␤,␥-rENaCs form a core conduction unit of epithelial Na ؉ channels and that interaction of these channels with other associated proteins, such as short actin filaments, confers regulation to channel activity.Membrane transport protein-cytoskeleton interactions are thought to be important not only for restricting various transporters to specific membrane domains, especially in epithelia, but also for regulating transport activity (1, 2). Actin networks interact with the plasma membrane either by direct binding (3, 4) or through anchoring proteins, including actin-binding protein (filamin), spectrin (fodrin, the non-erythroid form of spectrin), and ankyrin (5-8). The actin cytoskeleton has been shown to interact with a variety of transmembrane proteins, including ion transport molecules such as the band 3 anion exchanger (9), the epithelial Na ϩ /K ϩ -ATPase (6, 10), rat brain voltage-sensitive Na ϩ channels (11, 12), the Na ϩ -K ϩ -Cl Ϫ cotransporter (13), and the Na ϩ -H ϩ exchanger (14). Recently, functional interactions between the actin cytoskeleton and ion channels have been demonstrated for Na ϩ channel activity in epithelial cells (15), N-methyl-D-aspartic acid-activated channels in neurons (16), the Na ϩ /K ϩ -ATPase (17), a renal K ϩ channel (18), and two epithelial anion channels (namely, a renal Cl Ϫ channel (19) and the cystic fibrosis transmembrane conductance regulator (20, 21)). Apically located, renal amiloride-sensitive Na ϩ channels have also been shown to be associated directly with the actin-based membrane cytoskeleton (15, 22). Moreov...

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Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits

Cited by 1,850 publications

References 30 publications

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Mild dehydration: a risk factor of broncho-pulmonary disorders?

Regulation of Epithelial Sodium Channels by Short Actin Filaments

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