Acid-sensing (proton-gated) ion channels (ASICs)

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Acid-sensing ion channels (ASICs, provisional nomenclature; [27,48]) 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 [34] and INaC [35]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [22,26] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [23]). Splice variants of ASIC1[provisionally termed ASIC1a (ASIC, ASICα, BNaC2α) [44], ASIC1b (ASICβ, BNaC2β) [8] and ASIC1b2 (ASICβ2) [39]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [provisionally termed ASIC2a (MDEG1, BNaC1α, BNC1α) [21,33,45] and ASIC2b (MDEG2, BNaC1β) [28]] 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) [43], 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 down regulate the expression of ASIC1a and ASIC3 [1,16,24]. 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). The activation of ASIC1a within the central nervous system contributes to neuronal injury caused by focal ischemia [49] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [20]. However, activation of ASIC1a can terminate seizures [52]. Peripheral ASIC3-containing channels play a role in post-operative pain [12]. Further proposed roles for centrally and peripherally located ASICs are reviewed in [48] and [27]. The relationship of the cloned ASICs to endogenously expressed proton-gated ion channels is becoming established [14-15,19,25,27,29,38,46-48]. Heterologously expressed heteromultimers form ion channels with altered kinetics, ion selectivity, pH- sensitivity and sensitivity to blockers that resemble some of the native proton activated currents recorded from neurones [3,6,19,28].

Subunits

ASIC1 Show summary »

ASIC2 Show summary »

ASIC3 Show summary »

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How to cite this family page

Database page citation:

Acid-sensing (proton-gated) ion channels (ASICs). Accessed on 18/09/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=118.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA and Harmar AJ, CGTP Collaborators. (2013) The Concise Guide to PHARMACOLOGY 2013/14: Ligand-Gated Ion Channels. Br J Pharmacol. 170: 1582–1606.