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).

GtoImmuPdb view: OFF   

Overview

« Hide

Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [37]) 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 [47] and INaC [48] that have also been named BASICs, for bile acid-activated ion channels [59]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [6,32,36] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [34,58]). Splice variants of ASIC1 [provisionally termed ASIC1a (ASIC, ASICα, BNaC2α) [56], ASIC1b (ASICβ, BNaC2β) [14] and ASIC1b2 (ASICβ2) [51]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [provisionally termed ASIC2a (MDEG1, BNaC1α, BNC1α) [31,46,57] and ASIC2b (MDEG2, BNaC1β) [40]] 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) [55], 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 [2,24,33,39]. 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). Recent studies have shown that protons can act as neurotransmitters and that postsynaptically located ASICs of the CNS are involved in functions such as learning and fear perception [25,38,64]. The activation of ASIC1a within the central nervous system was shown to contribute to neuronal injury caused by focal ischemia [60] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [30]. However, activation of ASIC1a can terminate seizures [65]. Several studies pointed to a role of ASICs as peripheral sensors for inflammatory and post-operative pain [11,19-20,22]. ASIC1a has been shown to contribute at the level of the CNS to pain sensation [22,26,43]. Further proposed roles for centrally and peripherally located ASICs are reviewed in [1,12,28,35,37,58]. 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 [4,9,29,40].

Channels and Subunits

ASIC1 C Show summary »

ASIC2 C Show summary »

ASIC3 C Show summary »

Comments

Show »

Further reading

Show »

References

Show »

NC-IUPHAR subcommittee and family contributors

Show »

How to cite this family page

Database page citation:

Stephan Kellenberger, Laurent Schild. Acid-sensing (proton-gated) ion channels (ASICs). Accessed on 11/12/2017. 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.