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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).

Overview

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Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [2-3,39]) 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 [50] and INaC [51] that have also been named BASICs, for bile acid-activated ion channels [62]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [7,35,38] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [37,61]). Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [59], ASIC1b (ASICβ, BNaC2β) [17] and ASIC1b2 (ASICβ2) [54]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [34,49,60] and ASIC2b (MDEG2, BNaC1β) [44]] 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) [58], 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 [1,28,36,43]. 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 [29,40,67], responses to focal ischemia [63] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [33], as well as seizures [68] and pain [13,23-24,26]. 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 [5,11,32,44].

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

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Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie A, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. Br J Pharmacol. 176 Issue S1: S142-228.