Stefan Gründer

RWTH Aachen University · Institute of Physiology

Fast growing solid tumors are frequently surrounded by an acidic microenvironment. Tumor cells employ a variety of mechanisms to survive and proliferate under these harsh conditions. In that regard, acid-sensitive membrane receptors constitute a particularly interesting target, since they can affect cellular functions through ion flow and second me...

Fast growing solid tumors are frequently surrounded by an acidic microenvironment. Tumor cells employ a variety of mechanisms to survive and proliferate under these harsh conditions. In that regard, acid-sensitive membrane receptors constitute a particularly interesting target, since they can affect cellular functions through ion flow and second me...

It is increasingly appreciated that the acidic microenvironment of a tumour contributes to its evolution and clinical outcomes. However, our understanding of the mechanisms by which tumour cells detect acidosis and the signalling cascades that it induces is still limited. Acid-sensing ion channels (ASICs) are sensitive receptors for protons; theref...

Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be...

Acid-sensing ion channels (ASICs) are Na⁺ channels that are almost ubiquitously expressed in neurons of the brain. Functional ASIC1a is also expressed in glioblastoma stem cells, where it might sense the acidic tumor microenvironment. Prolonged acidosis induces cell death in neurons and reduces tumor sphere formation in glioblastoma via activation...

Acid-sensing ion channels (ASICs) sense extracellular protons and are involved in synaptic transmission and pain sensation. ASIC1a and ASIC3 are the ASIC subunits with the highest proton sensitivity. ASIC2a in contrast has low proton sensitivity but increases the variability of ASICs by forming heteromers with ASIC1a or ASIC3. ASICs are trimers and...

Acid-sensing ion channels (ASICs) are proton-gated ion channels that contribute to pain perception and neurotransmission. Being involved in sensing inflammation and ischemia, ASIC1a and ASIC3 are promising drug targets. Polyphenol tannic acid (TA) as well as green tea can interact with a variety of ion channels, but their effect on ASICs remains un...

Acid-sensing ion channels (ASICs) are Na ⁺ channels that are almost ubiquitously expressed in neurons of the brain. Functional ASIC1a is also expressed in glioblastoma stem cells, where it might sense the acidic tumor microenvironment. Prolonged acidosis induces cell death in neurons and reduces tumor sphere formation in glioblastoma via activation...

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na⁺ reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic ana...

The microenvironment of proliferative and aggressive tumours, such as the brain tumour glioblastoma multiforme (GBM), is often acidic, hypoxic, and nutrient deficient. Acid-sensing ion channels (ASICs) are proton-sensitive Na + channels that have been proposed to play a role in pH sensing and in modulation of cancer cell migration. We previously re...

Ion channels of the degenerin (DEG)/epithelial Na + channel (ENaC) family serve diverse functions ranging from mechanosensation over Na + reabsorption to H + sensing and neurotransmission. However, several diverse DEG/ENaCs interact with neuropeptides; some are directly activated, whereas others are modulated by neuropeptides. Two questions arise:...

Ion channels of the degenerin (DEG)/epithelial Na⁺ channel (ENaC) family serve diverse functions ranging from mechanosensation over Na⁺ reabsorption to H⁺ sensing and neurotransmission. However, several diverse DEG/ENaCs interact with neuropeptides; some are directly activated, whereas others are modulated by neuropeptides. Two questions arise: doe...

Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prol...

Background: Mutations in the Lamin A/C (LMNA) gene are responsible for about 6% of all familial dilated cardiomyopathy (DCM) cases which tend to present at a young age and follow a fulminant course. Methods: We report a 47-year-old DCM patient with severely impaired left ventricular ejection fraction and NYHA functional class IV despite optimal...

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na ⁺ reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic an...

Prolonged acidosis, as it occurs during ischemic stroke, induces neuronal death via acid-sensing ion channel 1a (ASIC1a). Concomitantly, it desensitizes ASIC1a, highlighting the pathophysiological significance of modulators of ASIC1a acid sensitivity. One such modulator is the opioid neuropeptide big dynorphin (Big Dyn) which binds to ASIC1a and en...

Acid-sensing ion channels (ASICs) are ionotropic receptors that are directly activated by protons. Although protons have been shown to act as a neurotransmitter and to activate ASICs during synaptic transmission, it remains a possibility that other ligands directly activate ASICs as well. Neuropeptides are attractive candidates for alternative agon...

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. They contribute to synaptic transmission, neuronal differentiation and neurodegeneration. ASICs have been mainly characterized in neurons from mice or rats and our knowledge of their properties in human neurons is scarce. Here, we functionally characterized ASICs in differentiating LU...

Hydra Na⁺ channels (HyNaCs) are peptide-gated ion channels of the DEG/ENaC gene family that are directly activated by neuropeptides of the Hydra nervous system. They have previously been successfully characterized in Xenopus oocytes. To establish their expression in mammalian cells, we transiently expressed heteromeric HyNaC2/3/5 in human HEK 293 a...

Neurons are excitable cells. They use ions and electrical signaling to talk to each to other, and when they talk to each other, neurons control behavior. The Oxford Handbook of Neuronal Ion Channels is an accessible reference describing the nature and properties of ion channels in neurons. The book explains how ion channels open and close, how they...

Extracellular adenosine triphosphate (ATP) regulates a broad variety of physiological functions in a number of tissues partly via ionotropic P2X receptors. Therefore, P2X receptors are promising targets for the development of therapeutically active molecules. Bile acids are cholesterol-derived amphiphilic molecules; their primary function is the fa...

Acid-sensing ion channels (ASICs) belong to the DEG/ENaC gene family. While ASIC1a, ASIC1b and ASIC3 are activated by extracellular protons, ASIC4 and the closely related bile acid-sensitive ion channel (BASIC or ASIC5) are orphan receptors. Neuropeptides are important modulators of ASICs. Moreover, related DEG/ENaCs are directly activated by neuro...

Acid-sensing ion channel 3 (ASIC3) is a proton-gated Na+ channel with important roles in pain. ASIC3 quickly desensitizes within less than a second, limiting its capacity to sense sustained acidosis during pain. RFamide neuropeptides are modulators of ASIC3 that slow its desensitization and induce a variable sustained current. The molecular mechani...

Neuropeptides commonly signal by metabotropic GPCRs. In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated ion channel and a GPCR. We identified and charact...

Acid-sensing ion channels (ASICs) are neuronal Na+channels that are activated by extracellular acidification. Inhibiting ASICs is neuroprotective in mouse models of ischemic stroke. As inhalational anesthetics interact with many ion channels and as some of them have neuroprotective effects, we hypothesized that inhalational anesthetics modulate ASI...

The bile acid-sensitive ion channel is activated by amphiphilic substances such as bile acids or artificial detergents via membrane alterations; however, the mechanism of membrane sensitivity of the bile acid-sensitive ion channel is not known. It has also not been systematically investigated whether other members of the degenerin/epithelial Na+cha...

Neuropeptides commonly signal by metabotropic G-protein coupled receptors (GPCRs). In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated channel and a GPCR....

Neuropeptides are one of the most diverse classes of signaling molecules and have attracted great interest over the years owing to their roles in regulation of a wide range of physiological processes. However, there are unique challenges associated with neuropeptide studies stemming from the highly variable molecular sizes of the peptides, low in v...

Acidic microenvironment is commonly observed in tumour tissues, including glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels, which are sensors of extracellular protons. Here we studied and functionally characterized ASICs in two primary gliob...

Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular protons. They contribute to the excitatory postsynaptic current and to the detection of painful acidosis. Moreover, they are activated during peripheral inflammation and acidosis associated with various neuronal disorders such as stroke and neuro-inflammation, rendering them...

Significance Marine cone snails provide one of the highest toxin diversities among venomous animals, the conotoxins, which often target ion channels. In addition, cone snail venoms contain short conopeptides, the molecular targets of which are mostly unknown. We identified a new conopeptide from the venom of the cone snail Conus textile that target...

The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple and thus have great potential to reveal fundamental principles of neural circuits. Unfortunately, cnidarians have thus far been relatively intractable to electrophysiological and genetic techniques and consequ...

Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of...

Acid Sensing Ion Channels (ASICs) detect extracellular proton signals and are involved in synaptic transmission and pain sensation. ASIC subunits assemble into homo- and heteromeric channels composed of three subunits. Single molecule imaging revealed that heteromers composed of ASIC1a and ASIC2a, which are widely expressed in the central nervous s...

Acid-sensing ion channels (ASICs) are voltage-independent proton-gated amiloride sensitive sodium channels, belonging to the DEG/ENaC gene family. Six different ASICs have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4) that are activated by a drop in extracellular pH, either as homo- or heteromers. An exception is ASIC4, which is no...

Pentafluorosulfanyl-containing analogs of flufenamic acid have been synthesized in high yields. Computationally, pKa, LogP and LogD values have been determined. Initial bioactivity studies reveal effects as ion channel modulators and inhibitory activities on aldo-keto reductase 1C3 (AKR1C3) as well as COX-1 and COX-2.

Neurons either use electrical or chemical synapses to communicate with each other. Transmitters at chemical synapses are either small molecules or neuropeptides. After binding to their receptors, transmitters elicit postsynaptic potentials, which can either be fast and transient or slow and longer lasting, depending on the type of receptor. Fast tr...

Acid-sensing ion channels (ASICs) are ligand-gated ion channels that are exquisitely sensitive to extracellular protons and can sense transient as well as sustained acidification. In this review, we will discuss activation and desensitization of ASICs by protons. We show that a linear reaction scheme can reproduce the basic electrophysiological pro...

The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological funct...

Background It is generally the case that fast transmission at neural synapses is mediated by small molecule neurotransmitters. The simple nervous system of the cnidarian Hydra, however, contains a large repertoire of neuropeptides and it has been suggested that neuropeptides are the principal transmitters of Hydra. An ion channel directly gated by...

Significance Our work concerns the stoichiometry of acid-sensing ion channels (ASICs), proton-gated Na ⁺ channels. In the central nervous system ASICs are composed of either only ASIC1a subunits or ASIC1a and ASIC2a subunits. Blockade of the ASIC1a/2a heteromer causes strong analgesia. Because ligands and drugs bind at subunit interfaces of ASICs,...

The DEG/ENaC gene family of ion channels is characterized by a high degree of structural similarity and an equally high degree of diversity concerning the physiological function. In humans and rodents, the DEG/ENaC family comprises 2 main subgroups: the subunits of the epithelial Na(+) channel (ENaC) and the subunits of the acid sensing ion channel...

The epithelial Na(+) channel (ENaC) is a key regulator of Na(+) absorption in various epithelia including the distal nephron and the distal colon. ENaC is a constitutively active channel, but its activity is modulated by a number of mechanisms. These include proteolytic activation, ubiquitination and cell surface expression, phosphorylation, intrac...

The human bile acid-sensitive ion channel (hBASIC) is a cation channel of the degenerin/epithelial Na(+) channel gene family that is expressed in the intestinal tract and can be activated by bile acids. Here, we show that in addition to its sensitivity for bile acids, hBASIC shares further key features with its rat ortholog: it is blocked by extrac...

TRPN1 is a candidate mechanotransduction channel in Drosophila and C. elegans, also present in hair cells of lower vertebrates. At its N-terminal cytoplasmic tail it contains 28 ankyrin repeats. We performed a yeast two-hybrid screen with the N-terminal ankyrin repeats of Xenopus TRPN1 as bait and identified the Penta-EF-hand protein peflin as a pu...

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic aci...

Degenerin/epithelial Na(+) channels (DEG/ENaCs) are Na(+) channels that are blocked by the diuretic amiloride. In general, they are impermeable for Ca(2+) or have a very low permeability for Ca(2+). We describe here, however, that a DEG/ENaC from the cnidarian Hydra magnipapillata, the Hydra Na(+) channel (HyNaC), is highly permeable for Ca(2+) (P(...

Of the three principal conformations of acid-sensing ion channels (ASICs) - closed, open and desensitized - only the atomic structure of the desensitized conformation had been known. Two recent papers report the crystal structure of chicken ASIC1 in complex with the spider toxin psalmotoxin 1, and one of these studies finds that, depending on the p...

Brain liver intestine Na(+) channel (BLINaC) is an ion channel of the DEG/ENaC gene family of unknown function. BLINaC from rats (rBLINaC) and humans (INaC) is inactive at rest, and its mode of activation has remained unclear. Here, we show that the BLINaC protein localizes to cholangiocytes, epithelial cells that line bile ducts. Moreover, we prov...

DEG/ENaC ion channels are trimeric proteins, forming a heterogeneous group of sodium-selective ion channels sensitive to the inhibitor amiloride. Most family members known so far are impermeable to calcium. Only ASIC 1a (and possibly MEC-4) conduct calcium to a minor extent. To identify ancient properties of this ion channel family, we have recentl...

The brain liver intestine Na(+) channel (BLINaC) is a member of the degenerin/epithelial Na(+) channel gene family of unknown function. Elucidation of the physiological function of BLINaC would benefit greatly from pharmacological tools that specifically affect BLINaC activity. Guided by the close molecular relation of BLINaC to acid-sensing ion ch...

Activation of acid-sensing ion channels (ASICs) contributes to neuronal death during stroke, to axonal degeneration during neuroinflammation, and to pain during inflammation. Although understanding ASIC gating may help to modulate ASIC activity during these pathologic situations, at present it is poorly understood. The ligand, H(+), probably binds...

Ion channels of the degenerin/epithelial Na+ channel gene family are Na+ channels that are blocked by the diuretic amiloride and are implicated in several human diseases. The brain liver intestine Na+ channel (BLINaC) is an ion channel of the degenerin/epithelial Na+ channel gene family with unknown function. In rodents, it is expressed mainly in b...

Acid-sensing ion channels (ASICs) are H(+)-gated Na(+) channels, which are present in most, if not all, neurons. The typical ASIC current is transient and is elicited by a rapid drop in the extracellular pH. In the human genome, four genes for ASICs are present: asic1 - 4. In this review, we will focus on ASIC1a, one of the key subunits in the cent...

Acid-sensing ion channels (ASICs) are proton-gated Na(+) channels. They are implicated in synaptic transmission, detection of painful acidosis, and possibly sour taste. The typical ASIC current is a transient, completely desensitizing current that can be blocked by the diuretic amiloride. ASICs are present in chordates but are absent in other anima...

Recently, three ion channel subunits of the degenerin (DEG)/epithelial Na(+) channel (ENaC) gene family have been cloned from the freshwater polyp Hydra magnipapillata, the Hydra Na(+) channels (HyNaCs) 2-4. Two of them, HyNaC2 and HyNaC3, co-assemble to form an ion channel that is gated by the neuropeptides Hydra-RFamides I and II. The HyNaC2/3 ch...

Recently we have identified five new ion channel subunits (HyNaC1-5) from Hydra magnipapillata that belong to the ENaC/DEG family of ion channels. We could show that the ion channel made out of HyNaC2/3/5 is gated directly by two endogeneous neuropeptides, the HydraRFamides I and II. Prominent human members of the ENaC/DEG family are the proton-gat...

Acid-sensing ion channels (ASICs) are cation-permeable membrane proteins activated by extracellular H+. They belong to the class of DEG/ENaC channels and share a common topology with cytosolic termini, two transmembrane domains and a large extracellular loop. ASICs are present in the genome of chordates but are absent in other animals. So far, func...

We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and d...

Stomatin is an integral membrane protein which is widely expressed in many cell types. It is accepted that stomatin has a unique hairpin-loop topology: it is anchored to the membrane with an N-terminal hydrophobic domain and the N- and C-termini are cytoplasmically localized. Stomatin is a prototype for a family of related proteins, containing amon...

ASICs (acid-sensing ion channels) are H(+)-gated Na(+) channels with a widespread expression pattern in the central and the peripheral nervous system. ASICs have a simple topology with two transmembrane domains, cytoplasmic termini and a large ectodomain between the transmembrane domains; this topology has been confirmed by the crystal structure of...

Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H+. H+ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H+ could in principle gate a channel by titration of a single amino acid. Experi...

Chemical transmitters are either low molecular weight molecules or neuropeptides. As a general rule, neuropeptides activate only slow metabotropic receptors. To date, only one exception to this rule is known, the FMRFamide-activated Na+ channel (FaNaC) from snails. Until now FaNaC has been regarded as a curiosity, and it was not known whether pepti...

There are four genes for acid-sensing ion channels (ASICs) in the genome of mammalian species. Whereas ASIC1 to ASIC3 form functional H+-gated Na+ channels, ASIC4 is not gated by H+, and its function is unknown. Zebrafish has two ASIC4 paralogs: zASIC4.1 and zASIC4.2. Whereas zASIC4.1 is gated by extracellular H+, zASIC4.2 is not. This differential...

The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel with important physiological functions and pathophysiological impact in the central nervous system. Here we show that homomeric ASIC1a is distinguished from other ASICs by a reduced response to successive acid stimulations. Such a reduced response is called tachyphylax...

Acid-sensing ion channels are excitatory receptors for extracellular H+. Since the extracellular H+ concentration can significantly increase during an inflammation, one of the proposed functions for ASICs is peripheral perception of pain. The ASIC1b and ASIC3 subunits are specifically expressed in sensory ganglia neurons and are candidate sensors o...

Acid-sensing ion channels (ASICs) are Na(+) channels gated by extracellular H(+). Six ASIC subunits that are expressed in neurons have been characterized. The tarantula toxin psalmotoxin 1 has been reported to potently and specifically inhibit homomeric ASIC1a and has been useful to characterize ASICs in neurons. Recently we have shown that psalmot...

In vertebrates, the senses of hearing and balance depend on hair cells, which transduce sounds with their hair bundles, containing actin-based stereocilia and microtubule-based kinocilia. A longstanding question in auditory science is the identity of the mechanically sensitive transduction channel of hair cells, thought to be localized at the tips...

Acid-sensing ion channels (ASICs) are ion channels activated by extracellular protons. They are involved in higher brain functions and perception of pain, taste, and mechanical stimuli. Homomeric ASIC1a is potently inhibited by the tarantula toxin psalmotoxin 1. The mechanism of this inhibition is unknown. Here we show that psalmotoxin 1 inhibits A...

Acid-sensing ion channels ASIC1a and ASIC1b are ligand-gated ion channels that are activated by H+ in the physiological range of pH. The apparent affinity for H+ of ASIC1a and 1b is modulated by extracellular Ca2+ through a competition between Ca2+ and H+. Here we show that, in addition to modulating the apparent H+ affinity, Ca2+ blocks ASIC1a in...

Acid-sensing ion channels (ASICs) are excitatory receptors for extracellular H(+). Proposed functions include synaptic transmission, peripheral perception of pain, and mechanosensation. Despite the physiological importance of these functions, the precise role of ASICs has not yet been established. In order to increase our understanding of the physi...

Acid-sensing ion channels (ASICs) are excitatory receptors for extracellular H+. Proposed functions include synaptic transmission, peripheral perception of pain, and mechanosensation. Despite the physiological importance of these functions, the precise role of ASICs has not yet been established. In order to increase our understanding of the physiol...

The epithelial Na+ channel (ENaC) is the apical entry pathway for Na+ in many Na+-reabsorbing epithelia. ENaC is a heterotetrameric protein composed of homologous alpha, beta, and gamma subunits. Mutations in ENaC cause severe hypertension or salt wasting in humans; and consequently, ENaC activity is tightly controlled. According to the concept of...

The mechanisms that establish behavioral, cognitive, and neuroanatomical asymmetries are poorly understood. In this study, we analyze the events that regulate development of asymmetric nuclei in the dorsal forebrain. The unilateral parapineal organ has a bilateral origin, and some parapineal precursors migrate across the midline to form this left-s...

Voltage-activated K(+) channels are important for shaping the receptor potentials of cochlear hair cells. In particular, the functional maturation of inner hair cells in mice around the onset of hearing coincides with the expression of a large, fast K(+) conductance, probably mediated by Ca(2+)-activated K(+) (BK) channels. In hearing organs of low...

Homomeric acid-sensing ion channel 1 (ASIC1) can be activated by extracellular H+ in the physiological pH range and may, therefore, contribute to neurotransmission and peripheral pain perception. ASIC1a and ASIC1b are alternative splice products of the ASIC1 gene. Here we show that both splice variants show steady-state inactivation when exposed to...

The purinergic P2X(7) receptor is an ATP-receptor channel predominantly expressed in immune cells. P2X(7) has been cloned from human, rat and mouse. Here we report cloning of the Xenopus laevis P2X(7) receptor (xP2X(7)). xP2X(7) is only about 50% identical to the mammalian homologues, shows a broad tissue expression pattern, and has the electrophys...

Acid-sensing ion channels (ASICs) are protongated Na(+) channels. They have been implicated with synaptic transmission, pain perception as well as mechanoperception. ASIC4 is the most recent member of this gene family. It shows expression throughout the central nervous system with strongest expression in pituitary gland. ASIC4 is inactive by itself...

Acid-sensing ion channels (ASICs) are activated by extracellular protons and are involved in neurotransmission in the central nervous system, in pain perception, as well as in mechanotransduction. Six different ASIC subunits have been cloned to date, which are encoded by four genes (ASIC1-ASIC4). Proton-gated currents have been described in isolate...

The P2X3 receptor is an ATP-gated ion channel predominantly expressed in nociceptive neurons from the dorsal root ganglion. P2X3 receptor channels are highly expressed in sensory neurons and probably contribute to the sensation of pain. Kinetics of P2X3 currents are characterized by rapid desensitization (<100 ms) and slow recovery (>20 s). Thus, a...

Endolymphatic ion composition in the adult inner ear is characterized by high K(+) and low Na(+) concentration. This unique ion composition is essential for proper functioning of sensory processing. Although a lot has been learned in recent years about molecules involved in K(+) transport in inner ear, the molecules involved in Na(+) transport are...

Major transporters and ion channels molecules in different parts of the kidney are responsible for some major monogenic forms of hereditary defects in salt homeostasis. One of the most illustrative examples is the case of the epithelial sodium channel ENaC. ENaC provides the apical entry mechanism for sodium in the distal nephron. Its activity is u...

Acid-sensing ion channels (ASICs) constitute a branch of the super-gene family of amiloride-sensitive sodium channels. So far five different ASICs have been cloned from mammalian tissues. They are activated by a drop of extracellular pH but differ with respect to effective agonist concentration, desensitization and mRNA expression pattern. Here we...

The epithelial Na+ channel (ENaC) is responsible for Na+ reabsorption in aldosterone target tissues such as distal nephron and colon. ENaC is a heterotetramer composed of three homologous subunits, alpha, beta, and gammaENaC. Mutations leading to loss of function or reduced channel activity have been identified in all three subunits in patients wit...

The autosomal recessive form of type I pseudohypoaldosteronism (PHA-I) is an inherited salt-losing syndrome resulting from diminution-of-function mutations in the 3 subunits of the epithelial Na+ channel (ENaC). A PHA-I stop mutation (alpha(R508stop)) of the ENaC alpha subunit is predicted to lack the second transmembrane domain and the intracellul...

The epithelial Na+ channel (ENaC) is responsible for Na+ reabsorption in aldosterone target tissues such as distal nephron and colon. ENaC is a heterotetramer composed of three homologous subunits, α, β, and γENaC. Mutations leading to loss of function or reduced channel activity have been identified in all three subunits in patients with pseudohyp...

One of the characteristic features of the structure of the epithelial sodium channel family (ENaC) is the presence of two highly conserved cysteine-rich domains (CRD1 and CRD2) in the large extracellular loops of the proteins. We have studied the role of CRDs in the functional expression of rat alphabetagamma ENaC subunits by systematically mutatin...