A new member of acid-sensing ion channels from pituitary gland

Gründer, Stefan; Hs, Geissler; El, Bässler; Jp, Ruppersberg

doi:10.1097/00001756-200006050-00003

Cited by 215 publications

(189 citation statements)

References 2 publications

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“…ASIC4 subunits show high level of expression in pituitary gland. Similar to ASIC2b, they do not seem to form functional homomeric channels [30,31].…”

Section: Tissue Distribution and Electrophysiological Properties Of Amentioning

confidence: 98%

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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“…ASIC4 subunits show high level of expression in pituitary gland. Similar to ASIC2b, they do not seem to form functional homomeric channels [30,31].…”

Section: Tissue Distribution and Electrophysiological Properties Of Amentioning

confidence: 98%

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

show abstract

“…These, too, have unique N termini and share the C-terminal amino acids (11). Splice variants have not yet been identified for ASIC3 (DRASIC) (12,13) and ASIC4 (SPASIC) (14,15). Except for ASIC2b and ASIC4, all subunits have the ability to form functional homomeric channels when expressed in Xenopus laevis oocytes or mammalian cells.…”

mentioning

confidence: 99%

pH Dependency and Desensitization Kinetics of Heterologously Expressed Combinations of Acid-sensing Ion Channel Subunits

Hesselager

Timmermann

Ahring

2004

Journal of Biological Chemistry

297

347

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The exact subunit combinations of functional native acid-sensing ion channels (ASICs) have not been established yet, but both homomeric and heteromeric channels are likely to exist. To determine the ability of different subunits to assemble into heteromeric channels, a number of ASIC1a-, ASIC1b-, ASIC2a-, ASIC2b-, and ASIC3-containing homo-and heteromeric channels were studied by whole-cell patch clamp recordings with respect to pH sensitivity, desensitization kinetics, and level of sustained current normalized to peak current. Analyzing and comparing data for these three features demonstrated unique heteromeric channels in a number of co-expression experiments. Formation of heteromeric ASIC1a؉2a and ASIC1b؉2a channels was foremost supported by the desensitization characteristics that were independent of proton concentration, a feature none of the respective homomeric channels has. Several lines of evidence supported formation of ASIC1a؉3, ASIC1b؉3, and ASIC2a؉3 heteromeric channels. The most compelling was the desensitization characteristics, which, besides being proton-independent, were faster than those of any of the respective homomeric channels. ASIC2b, which homomerically expressed is not activated by protons per se, did not appear to form unique heteromeric combinations with other subunits and in fact appeared to suppress the function of ASIC1b. Co-expression of three subunits such as ASIC1a؉2a؉3 and ASIC1b؉2a؉3 resulted in data that could best be explained by coexistence of multiple channel populations within the same cell. This observation seems to be in good agreement with the fact that ASIC-expressing sensory neurons display a variety of acid-evoked currents.It is well established that tissue acidification, which may be present in inflammatory and ischemic conditions, causes pain (1-3). In line with this, peripheral sensory neurons exhibit sensitivity toward acid by activating several types of depolarizing currents (4 -6). Although the repertoire of ion channels responsible for these currents is not fully known, the family of acid-sensing ion channels (ASICs) 1 is believed to be an important constituent. The ASIC family is a member of the ENaC/ DEG superfamily, which also includes the amiloride-sensitive epithelial sodium channels (ENaCs), the mechanically gated degenerins of Caenorhabditis elegans (DEGs), and a neuropeptide-gated channel of Helix aspersa (FaNaC). The membrane topology of all channels within this superfamily comprises two transmembrane domains, intracellular N and C termini and a large extracellular loop with a number of conserved cysteine residues (7). Currently, four genes encoding six ASIC transcripts have been cloned and characterized from mammalian organisms. ASIC1a (BNaC2) and ASIC1b (ASIC1␤) are the products of alternatively spliced transcripts of the ASIC1 gene that differ in the N-terminal region, including the first transmembrane domain and the proximal part of the large extracellular domain (8 -10). ASIC2a (BNaC1, MDEG) and ASIC2b (MDEG2) are alternatively spliced forms of ...

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“…2 The three polymorphisms we identified map to a region, which shows comparatively high sequence divergence. This may indicate that these polymorphisms do not interfere with normal channel activity.…”

Section: Discussionmentioning

confidence: 92%

“…It shows a rather restricted expression pattern with strongest expression in pituitary gland. 2 But low level of expression is observed throughout the CNS. It is inactive by itself and the physiological role of this channel is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia

et al. 2001

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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 and its function is unknown. Mutations in ion channel subunits, which are homologues of ASICs lead to neurodegeneration in Caenorhabditis elegans. It has, therefore, been speculated that similar mutations in ASICs may be responsible for neurodegeneration in humans. Here, we show that ASIC4 maps to the long arm of chromosome 2 in close proximity to the locus for paroxysmal dystonic choreoathetosis (PDC), a movement disorder with unknown cause. Ion channel genes have been shown to cause several other paroxysmal neurologic disorders and are important candidate genes for PDC. We established the genomic organisation of the ASIC4 gene and screened a PDC pedigree for mutations in the coding region. Although we identified three polymorphisms in the Cterminal part of the ASIC4 protein, these were not present in each affected subject in the PDC kindred we analysed. Therefore, although the ASIC4 gene is physically mapped to the PDC locus, our data indicates that ASIC4 gene mutation is not the cause of PDC. It remains to be established if mutations in ASIC4 or other ASIC subunits may cause neurological disorders. European Journal of Human Genetics (2001) 9, 672 ± 676.

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A new member of acid-sensing ion channels from pituitary gland

Cited by 215 publications

References 2 publications

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

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

pH Dependency and Desensitization Kinetics of Heterologously Expressed Combinations of Acid-sensing Ion Channel Subunits

Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia

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