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

Gründer, Stefan; Geisler, Hyun Soon; Rainier, Shirley; Fink, John K.

doi:10.1038/sj.ejhg.5200699

Cited by 14 publications

(11 citation statements)

References 24 publications

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“…Using RT-PCR and the appropriately designed primers, we sequenced the entire coding region of ASIC1 from these cells. From the sequence analysis, we determined that there was no gain-of-function in positions that have previously been described, namely, Gly 433 (ASIC1) or Gly 430 (ASIC2) (7,17,18). The results of these experiments demonstrate that obvious gain-of-function mutations do not occur in ASIC1.…”

Section: Gain-of-function Point Mutations In Asic1 Isolated From Braimentioning

confidence: 54%

“…Moreover, ASIC4 is inactive by itself and hence is not thought to encode a proton-gated ion channel (6,7). Although the subunit composition of brain Na ϩ channels in native tissues is unknown, evidence for heteromultimeric channel formation with distinctive functional characteristics has been obtained (7)(8)(9)(10). These brain Na ϩ channels, like their epithelial counterparts, can be inhibited by amiloride and its analogs, although with a much lower affinity (11).…”

mentioning

confidence: 98%

“…Hence, these channels may function as acid pH sensors in normal brain and in pathophysiological states such as ischemia or epilepsy where tissue acidification occurs (15,16). Gain-of-function mutations of ASIC1 and ASIC2 have also been detected and have been proposed to participate in neurodegenerative disease (7,17,18). The function of these channels in glia remains a mystery, yet functional amiloride-sensitive Na ϩ current expression selectively characterizes high grade gliomas.…”

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confidence: 99%

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Acid-sensing Ion Channels in Malignant Gliomas

Berdiev

Xia

McLean

et al. 2003

Journal of Biological Chemistry

128

134

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High grade glioma cells derived from patient biopsies express an amiloride-sensitive sodium conductance that has properties attributed to the human brain sodium channel family, also known as acid-sensing ion channels (ASICs). This amiloride-sensitive conductance was not detected in cells obtained from normal brain tissue or low grade or benign tumors. Differential gene profiling data showed that ASIC1 and ASIC2 mRNA were present in normal and low grade tumor cells. Although ASIC1 was present in all of the high grade glial cells examined, ASIC2 mRNA was detected in less than half. The main purpose of our work was to examine the molecular mechanisms that may underlie the constitutively activated sodium currents present in high grade glioma cells. Our results show that 1) gain-of-function mutations of ASIC1 were not present in a number of freshly resected and cultured high grade gliomas, 2) syntaxin 1A inhibited ASIC currents only when ASIC1 and ASIC2 were co-expressed, and 3) the inhibition of ASIC currents by syntaxin 1A had an absolute requirement for either ␥-or ␦-hENaC. Transfection of cultured cells originally derived from high grade gliomas (U87-MG and SK-MG1) with ASIC2 abolished basal amiloride-sensitive sodium conductance; this inhibition was reversed by dialysis of the cell interior with Munc-18, a syntaxinbinding protein that typically blocks the interaction of syntaxin with other proteins. Thus, syntaxin 1A cannot inhibit Na ؉ permeability in the absence of adequate plasma membrane ASIC2 expression, accounting for the observed functional expression of amiloride-sensitive currents in high grade glioma cells.

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Section: Gain-of-function Point Mutations In Asic1 Isolated From Braimentioning

confidence: 54%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Acid-sensing Ion Channels in Malignant Gliomas

Berdiev

Xia

McLean

et al. 2003

Journal of Biological Chemistry

128

134

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“…(3)). The isoforms are coded by four different genes, two of them spliced in two variants: ASIC1a and ASIC1b, ASIC2a and ASIC2b, ASIC3 and ASIC4 [46][47][48][49][50][51][52]. Each isoform is a protein of 510 to 560 amino acids along with two transmembrane domains and a large extracellular loop.…”

Section: Acid Sensing Ion Channels Are Sensors Of Tissue Acidosismentioning

confidence: 99%

Acid-Sensing Ion Channels (ASICs): New Targets for the Analgesic Effects of Non-Steroid Anti-Inflammatory Drugs (NSAIDs)

Voilley

2004

CDTIA

155

111

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Non-steroid anti-inflammatory drugs (NSAIDs) are major drugs used in the treatment of inflammation and pain in a wide variety of disorders. NSAIDs constitute a diverse group of chemicals, categorized according to their chemical structures that share the same therapeutic properties. Among the main compounds are aspirin and salicylate, diclofenac and flurbiprofen. The best-known mechanism of action of NSAIDs is the inhibition of prostaglandin synthesis secondary to their action on cyclooxygenases (COXs). However, data have been accumulating through the years indicating that NSAIDs also act on other targets to counteract pain. Their analgesic effects are not necessarily the consequence of their anti-inflammatory action. Administration of NSAIDs reduces cutaneous and corneal pain induced by acidic pH in the absence of inflammation. Tissue acidosis, which is a dominant factor in inflammation, tumors and ischemia, has an important contribution in pain and hyperalgesia. This is due to direct excitation of the nociceptive sensory neurons by protons-gated depolarizing currents. Actually, these neurons bear a major category of ion channels that are sensitive to extracellular pH changes, the acid-sensing ion channels (ASICs). ASIC channels are able to induce action potential triggering on sensory neurons after a moderate extracellular pH decrease. They undergo transcriptional induction and post-translational regulation during inflammation and thus participate in the hypersensitization of the nociceptive system in this physiopathological condition. One specific ASIC isoform is also thought to mediate cardiac ischemic pain. COX-independent direct inhibition of their activity by different NSAIDs has been shown to occur at therapeutic doses of these compounds, on native ASIC currents on sensory neurons, as well as on ASIC channels expressed in heterologous systems. Moreover, NSAIDs also prevent the large inflammation-induced increase of their expression. These two effects are thus proposed to play an important role in the analgesic effects of NSAIDs in addition to their well-known action through COXs, and particularly in case of inflammation.

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“…Their expression and activity are induced by inflammation (Voilley et al, 2001;Mamet et al, 2002Mamet et al, , 2003 and are directly inhibited by nonsteroid anti-inflammatory drugs (Voilley et al, 2001;Voilley, 2004). Functional ASICs are homomeric or heteromeric tetramers made of isoforms encoded by four different genes, two of them spliced in two variants: ASIC1a and ASIC1b, ASIC2a and ASIC2b, and ASIC3 and ASIC4 (Waldmann et al, 1996;Garcia-Anoveros et al, 1997;Lingueglia et al, 1997;Waldmann et al, 1997a,b;Chen et al, 1998;Akopian et al, 2000;Grunder et al, 2001). Their properties vary according to their subunit composition.…”

Section: Introductionmentioning

confidence: 99%

Silencing Acid-Sensing Ion Channel 1a Alters Cone-Mediated Retinal Function

Ettaiche¹,

Deval²,

Cougnon³

et al. 2006

J. Neurosci.

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The action of extracellular protons on retinal activity and phototransduction occurs through pH-sensitive elements, mainly membrane conductances present on the different cell types of the outer and inner nuclear layers and of the ganglion cell layer. Acid-sensing ion channels (ASICs) are depolarizing conductances that are directly activated by protons. We investigated the participation of ASIC1a, a particular isoform of ASICs, in retinal physiology in vivo using electroretinogram measurements. In situ hybridization and immunohistochemistry localized ASIC1a in the outer and inner nuclear layers (cone photoreceptors, horizontal cells, some amacrine and bipolar cells) and in the ganglion cell layer. Both the in vivo knockdown of ASIC1a by antisense oligonucleotides and the in vivo blocking of its activity by PcTx1, a specific venom peptide, were able to decrease significantly and reversibly the photopic a-and b-waves and oscillatory potentials. Our study indicates that ASIC1a is an important channel in normal retinal activity. Being present in the inner segments of cones and inner nuclear layer cells, and mainly at synaptic cleft levels, it could participate in gain adaptation to ambient light of the cone pathway, facilitating cone hyperpolarization in brightness and modulating synaptic transmission of the light-induced visual signal.

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

Cited by 14 publications

References 24 publications

Acid-sensing Ion Channels in Malignant Gliomas

Acid-sensing Ion Channels in Malignant Gliomas

Acid-Sensing Ion Channels (ASICs): New Targets for the Analgesic Effects of Non-Steroid Anti-Inflammatory Drugs (NSAIDs)

Silencing Acid-Sensing Ion Channel 1a Alters Cone-Mediated Retinal Function

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