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

Wiemuth, Dominik; Assmann, Marc; Gründer, Stefan

doi:10.4161/chan.27493

Cited by 44 publications

(43 citation 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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“…ASIC5 is the most divergent member of the family and it forms an ion channel that is insensitive to protons but is sensitive to bile acids. Therefore, it was named as bile acid‐sensitive ion channel (BASIC) (Table ) . Homologs of ASICs are also found in chordates and early vertebrates such as lamprey and shark, but in contrast to most mammalian homologs, these appear to be insensitive to protons .…”

Section: Introductionmentioning

confidence: 99%

ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters

Hanukoglu

2016

The FEBS Journal

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The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na + ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part. In most vertebrates, there are five paralogous genes that code for ASICs (ASIC1-ASIC5), and four for ENaC subunits alpha, beta, gamma, and delta (a, b, c, and d). While ASICs can form functional channels as a homo-or heterotrimer, ENaC functions as an obligate heterotrimer composed of a-b-c or b-c-d subunits. The structure of ASIC has been determined in several conformations, including desensitized and open states. This review presents a comparison of the structures of these states using easy-to-understand molecular models of the full complex, the central tunnel that includes an outer vestibule, the channel pore, and ion selectivity filter. The differences in the secondary, tertiary, and quaternary structures of the states are summarized to pinpoint the conformational changes responsible for channel opening. Results of site-directed mutagenesis studies of ENaC subunits are examined in light of ASIC1 models. Based on these comparisons, a molecular model for the selectivity filter of ENaC is built by in silico mutagenesis of an ASIC1 structure. These models suggest that Na + ions pass through the filter in a hydrated state.

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Acid-sensing (proton-gated) ion channels (ASICs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019

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Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [35]) are members of a Na + channel superfamily that includes the epithelial Na + channel (ENaC), the FMRF-amide activated channel (FaNaC) of invertebrates, the degenerins (DEG) of Caenorhabitis elegans, channels in Drosophila melanogaster and 'orphan' channels that include BLINaC [46] and INaC [47] that have also been named BASICs, for bile acidactivated ion channels [58]. ASIC subunits contain two TM domains and assemble as homo-or hetero-trimers [34,31,5] to form proton-gated, voltage-insensitive, Na + permeable, channels (reviewed in [ 33,57]). Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [55], ASIC1b (ASICβ, BNaC2β) [13] and ASIC1b2 (ASICβ2) [50]; note that ASIC1a is also permeable to Ca 2+ ] and ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [45, 56, 30] and ASIC2b (MDEG2, BNaC1β) [40]] have been cloned. Unlike ASIC2a (listed in table), heterologous expression of ASIC2b alone does not support H + -gated currents. A third member, ASIC3(DRASIC, TNaC1) [54], has been identified. A fourth mammalian member of the family (ASIC4/SPASIC) does not support a proton-gated channel in heterologous expression systems and is reported to downregulate the expression of ASIC1a and ASIC3 [1,32,24,39]. ASIC channels are primarily expressed in central and peripheral neurons including nociceptors where they participate in neuronal sensitivity to acidosis. They have also been detected in taste receptor cells (ASIC1-3), photoreceptors and retinal cells (ASIC1-3), cochlear hair cells (ASIC1b), testis (hASIC3), pituitary gland (ASIC4), lung epithelial cells (ASIC1a and -3), urothelial cells, adipose cells (ASIC3), vascular smooth muscle cells (ASIC1-3), immune cells (ASIC1,-3 and -4) and bone (ASIC1-3). A neurotransmitter-like function of protons has been suggested, involving postsynaptically located ASICs of the CNS in functions such as learning and fear perception [25,36,63], responses to focal ischemia [59] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [ 29], as well as seizures [64] and pain [19,20,10,22]. Heterologously expressed heteromultimers form ion channels with differences in kinetics, ion selectivity, pH-sensitivity and sensitivity to blockers that resemble some of the native proton activated currents recorded from neurones [40,3,28,8].

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

Cited by 44 publications

References 47 publications

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

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

ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters

Acid-sensing (proton-gated) ion channels (ASICs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

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