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

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M. T.; Wasmuth, Hermann E.; Gründer, Stefan

doi:10.4161/chan.22406

Cited by 27 publications

(25 citation statements)

References 21 publications

(30 reference statements)

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“…BASIC is closely related to ASICs and seems to be restricted to mammals. It is activated by millimolar concentrations of bile acids (Wiemuth et al, 2012;Wiemuth et al, 2013a;Wiemuth et al, 2013b), but at present it is not clear whether bile acids are the natural stimulus to open the channel. In rodents, BASIC is also expressed in the brain (Sakai et al, 1999;Boiko et al, 2014) where concentrations of bile acids are not high enough to activate the channel.…”

Section: Reviewmentioning

confidence: 99%

Peptide-gated ion channels and the simple nervous system of Hydra

Gründer

Assmann

2015

Journal of Experimental Biology

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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 transient potentials are mediated by ionotropic receptors and slow long-lasting potentials by metabotropic receptors. Transmitters and receptors are well studied for animals with a complex nervous system such as vertebrates and insects, but much less is known for animals with a simple nervous system like Cnidaria. As cnidarians arose early in animal evolution, nervous systems might have first evolved within this group and the study of neurotransmission in cnidarians might reveal an ancient mechanism of neuronal communication. The simple nervous system of the cnidarian Hydra extensively uses neuropeptides and, recently, we cloned and functionally characterized an ion channel that is directly activated by neuropeptides of the Hydra nervous system. These results demonstrate the existence of peptide-gated ion channels in Hydra, suggesting they mediate fast transmission in its nervous system. As related channels are also present in the genomes of the cnidarian Nematostella, of placozoans and of ctenophores, it should be considered that the early nervous systems of cnidarians and ctenophores have co-opted neuropeptides for fast transmission at chemical synapses.

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Section: Reviewmentioning

confidence: 99%

Peptide-gated ion channels and the simple nervous system of Hydra

Gründer

Assmann

2015

Journal of Experimental Biology

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“…Consequently, the removal of divalent cations induces robust currents. [24][25][26] Apparent affinities of rat BASIC for Ca 2+ and Mg 2+ are 13 and 79 μM, 24,26 respectively, and of human BASIC 18 and 51 μM, 25 respectively. Under normal physiological conditions these channels would always be in an inactive, nearly silent state.…”

Section: Pharmacological Characteristics Of Basicmentioning

confidence: 99%

“…33 In a follow-up study, ursodeoxycholic acid (UDCA), which is used to treat various liver diseases including gallstones and primary biliary cirrhosis, 34 was also shown to potently activate BASIC with a similar apparent affinity (EC 50 : 2.5 mM) as HDCA. 26 In a recent study, human BASIC was characterized on the single channel level. Different from observations in whole oocytes, human BASIC was highly selective for Na + .…”

Section: Are Bile Acids Natural Ligands Of Basic?mentioning

confidence: 99%

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

Wiemuth

Assmann

Gründer³

2013

Channels

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“…2A) of rBASIC, and we analyzed their effect by activating the channels successively by the removal of extracellular divalent cations (ϪCa 2ϩ ) and the application of 2 mM UDCA (Fig. 2), a potent activator of rat and human BASIC (19).…”

Section: Removal Of the Cytosolic N-terminal Region Of Rbasicmentioning

confidence: 99%

“…BASIC represents a third subgroup within the human and rodent Deg/ ENaC family (3) and is sometimes referred to as ASIC5 (15), although it is not sensitive to protons (16,17). Instead, BASIC is activated by millimolar concentrations of bile acids (18,19).…”

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

Schmidt

Löhrer

Alsop

et al. 2016

Journal of Biological Chemistry

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Edited by George CarmanThe 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. The physiological function of BASIC, however, is unknown. Deg/ ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic ␣-helical structure within its N-terminal domain. This ␣-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction.

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

Cited by 27 publications

References 21 publications

Peptide-gated ion channels and the simple nervous system of Hydra

Peptide-gated ion channels and the simple nervous system of Hydra

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

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

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