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

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).

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Overview

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Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [32]) 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 [41] and INaC [42] that have also been named BASICs, for bile acid-activated ion channels [53]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [5,28,31] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [30,52]). Splice variants of ASIC1 [provisionally termed ASIC1a (ASIC, ASICα, BNaC2α) [50], ASIC1b (ASICβ, BNaC2β) [12] and ASIC1b2 (ASICβ2) [45]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [provisionally termed ASIC2a (MDEG1, BNaC1α, BNC1α) [27,40,51] and ASIC2b (MDEG2, BNaC1β) [35]] 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) [49], 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 [1,22,29,34]. 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 [23,33,58], responses to focal ischemia [54] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [26], as well as seizures [59] and pain [10,17-18,20]. 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 [3,8,25,35].

Channels and Subunits

ASIC1 C Show summary » More detailed page

ASIC2 C Show summary » More detailed page

ASIC3 C Show summary » More detailed page

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Stephan Kellenberger, Laurent Schild. Acid-sensing (proton-gated) ion channels (ASICs). Accessed on 11/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=118.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Peters JA, Kelly E, Marrion NV, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Ligand-gated ion channels. Br J Pharmacol. 174 Suppl 1: S130-S159.