Disease relevance of ACCN3

• 4. CIPP mRNA is found at a significant level in the same dorsal root ganglion neuronal cell population that expresses the ASIC3 subunit, i.e. mainly in the small nociceptive neurons [1].
• Because acidic luminal fluid in the cystic fibrosis airway and lung tends to stimulate ASIC3 channel expression and activity, the interaction of ASIC3 and CFTR may contribute to defective salt and fluid transepithelial transport in the cystic fibrotic pulmonary system [2].
• The ASIC1b and ASIC3 subunits are specifically expressed in sensory ganglia neurons and are candidate sensors of peripheral acidosis [3].
• This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia [4].
• Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia [5].

High impact information on ACCN3

• Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of the degenerins/epithelial sodium channel (DEG/ENaC) receptor family is expressed predominantly in sensory neurons including nociceptive neurons responding to protons [6].
• On the other hand, cAMP-activated CFTR activity was significantly inhibited following constitutive activation of putative ASIC3 at pH 6 [2].
• ASIC3 and these interacting proteins were expressed in dorsal root ganglia and spinal cord, and PSD-95 co-precipitated ASIC3 from spinal cord [7].
• The finding that multiple PDZ-containing proteins bind ASIC3 and can influence its presence in the plasma membrane suggests that they may play an important role in the contribution of ASIC3 to nociception and mechanosensation [7].
• The acid-sensing ion channel-3 (ASIC3) is a degenerin/epithelial sodium channel expressed in the peripheral nervous system [7].

Biological context of ACCN3

• Using RT-PCR and mRNA blot hybridization, we detected hASIC3 mRNA in sensory ganglia, brain, and many internal tissues including lung and testis, so hASIC3 gene expression was not restricted to peripheral sensory neurons [8].
• The biphasic desensitisation kinetics and the sequence homology suggest that this novel clone (hASIC3) is the human orthologue of rASIC3 (rDRASIC) [9].
• We localised the hASIC3 gene to the human chromosome 7q35, 6.4 cRad telomeric from the microsatellite AFMA082XC9 [9].
• The normal mouse ACCN3 cDNA and an alternatively spliced transcript were elucidated by reverse transcription polymerase chain reaction from mouse inner ear RNA [10].
• Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats [11].

Anatomical context of ACCN3

• To investigate the subunit composition of native ASICs in peripheral and central neurons, we co-injected human as well as rodent ASIC2a and ASIC3 subunits in Xenopus oocytes [12].
• In addition, significant levels of ASIC1 and ASIC3 mRNA were found in skeletal muscle tissue samples [13].
• We have cloned a new member of this superfamily from human testis, which was named hTNaC1 (for human testis sodium channel 1) [14].
• In bone, ASIC2 and ASIC3 were most abundant, while in chondrocytes it was ASIC1 [15].
• Indirect immunofluorescence microscopy revealed that ASIC3 was co-segregated with CFTR in the apical membranes of Calu-3 cells [2].

Associations of ACCN3 with chemical compounds

• The sensitivity to pH or amiloride of single versus co-expressed ASIC subunits was not significantly different; however, gadolinium ions inhibited ASIC3 and ASIC2a+3 responses with much higher potency (IC(50) approximately 40 microm) than the ASIC2a response (IC(50) >/=1 mm) [12].
• Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid [4].
• Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons [4].
• Finally, the effect of lidocaine on pain and ASIC3 expression in the disc herniation model was examined [11].

Other interactions of ACCN3

• RT-PCR revealed that all these cell types expressed TRPV1 (VR1), ASIC1a, and ASIC3 subunits of proton-gated ion channels [16].
• ASIC2b, ASIC3, and ASIC4 were expressed to a lesser degree in vestibular ganglion neurons [17].

Analytical, diagnostic and therapeutic context of ACCN3

• We describe here the molecular cloning of a novel human proton receptor, hASIC3, a 531-amino acid-long subunit homologous to rat DRASIC [8].
• 0. Immunoassays showed that both ASIC3 and CFTR proteins were expressed and co-immunoprecipitated mutually in Calu-3 cells [2].
• Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured [18].
• Circular dichroism spectra of BcIII and BcIV show a high content of beta-strand secondary structure in both peptides, very similar to type 1 sodium channel toxins from various sea anemones, and to APETx1 and APETx2 from A. elegantissima, a HERG channel modulator and an ASIC3 inhibitor, respectively [19].

References