The bile acid-sensitive ion channel (BASIC) mediates bile acid-dependent currents in bile duct epithelial cells.

The bile acid-sensitive ion channel (BASIC) is a member of the Deg/ENaC family of ion channels that is activated by bile acids. Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of BASIC in these cell types is not yet understood. Here we used a cholangiocyte cell line, normal rat cholangiocytes (NRCs), which expresses BASIC to study the role of the channel in epithelial transport using Ussing chamber experiments.

The Neuropeptide Nocistatin Is Not a Direct Agonist of Acid-Sensing Ion Channel 1a (ASIC1a).

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 agonists of ASICs, because related ionotropic receptors are directly activated by neuropeptides and because diverse neuropeptides modulate ASICs.

The mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K channel Kv1.1 through protein kinase C delta.

Background: ADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases.

Bile acids are potent inhibitors of rat P2X2 receptors.

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 facilitation of efficient nutrient fat digestion.

Screening of 109 neuropeptides on ASICs reveals no direct agonists and dynorphin A, YFMRFamide and endomorphin-1 as modulators.

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.

Comparative electrophysiological analysis of the bile acid-sensitive ion channel (BASIC) from different species suggests similar physiological functions.

Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of the bile acid-sensitive ion channel (BASIC) remains unknown. Rat BASIC (rBASIC) and mouse BASIC (mBASIC) share 97% of their amino acid sequence but show strikingly different biophysical properties. rBASIC is inactive at rest while mBASIC is constitutively active, when expressed in Xenopus oocytes.

Inhalational anesthetics accelerate desensitization of acid-sensing ion channels.

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 ASICs.

Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane Alterations.

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 channel (DEG/ENaC) gene family are affected by amphiphilic compounds. Here, we show that DEG/ENaCs ASIC1a, ASIC3, ENaC, and the purinergic receptor P2X2 are modulated by a large number of different, structurally unrelated amphiphilic substances, namely the detergents N-lauroylsarcosine, Triton X-100, and β-octylglucoside; the fenamate flufenamic acid; the antipsychotic drug chlorpromazine; the natural phenol resveratrol; the chili pepper compound capsaicin; the loop diuretic furosemide; and the antiarrythmic agent verapamil.

The ALS-linked E102Q mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins.

Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway.

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel.

Pentafluorosulfanyl-containing flufenamic acid analogs: Syntheses, properties and biological activities.

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.

The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.

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 bile acid-sensitive ion channel (BASIC), the ignored cousin of ASICs and ENaC.

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 channels (ASICs). The bile acid-sensitive channel (BASIC), previously known as BLINaC or INaC, represents a third subgroup within the DEG/ENaC family.

Bile acids increase the activity of the epithelial Na+ 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, intracellular Na(+) concentration, and shear stress.

Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC).

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 extracellular divalent cations, is inhibited by micromolar concentrations of the diarylamidine diminazene, and activated by millimolar concentrations of flufenamic acid. Furthermore, we demonstrate that two major bile acids present in human bile, chenodeoxycholic acid and deoxycholic acid, activate hBASIC in a synergistic manner.

Transient receptor potential N (TRPN1) from Xenopus interacts with the penta-EF-hand protein peflin.

TRPN1 is a candidate mechanotransduction channel in Drosophila and Caenorhabditis 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 putative interaction partner.

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid.

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 acid, as agonists of rBASIC.

BASIC--a bile acid-sensitive ion channel highly expressed in bile ducts.

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.

The pharmacological profile of brain liver intestine Na+ channel: inhibition by diarylamidines and activation by fenamates.

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 channels, we discovered in this study that rat BLINaC (rBLINaC) and mouse BLINaC are inhibited by micromolar concentrations of diarylamidines and nafamostat, similar to acid-sensing ion channels.

Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium channel regulation.

Background: The epithelial sodium channel (ENaC) is an integral component of the pathway for Na(+) absorption in epithelial cells. The ubiquitin ligases Nedd4 and Nedd4-2 bind to ENaC and decrease its activity. Conversely, Serum- and Glucocorticoid regulated Kinase-1 (SGK1), a downstream mediator of aldosterone, increases ENaC activity.

A single amino acid tunes Ca2+ inhibition of brain liver intestine Na+ channel (BLINaC).

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 brain, liver, and intestine, and to a lesser extent in kidney and lung.

Epithelial sodium channel (ENaC) is multi-ubiquitinated at the cell surface.

The human ENaC (epithelial sodium channel), a complex of three subunits, provides the rate-limiting step for sodium uptake in the distal nephron, and therefore plays a key role in salt homoeostasis and in regulating blood pressure. The number of active sodium channel complexes present at the plasma membrane appears to be tightly controlled. In Liddle's syndrome, a form of hypertension caused by an increase in the number of active sodium channels at the cell membrane, the betaENaC or gammaENaC subunit gene contains a mutation that disrupts the binding site for the Nedd4 (neuronal precursor cell expressed developmentally down-regulated gene 4) family of ubiquitin-protein ligases.