ASIC1a | acid-sensing Ion Channel 1 Isoform 2
Acid-sensing ion channels, member of the ENaC/Degenerin superfamily
Members and topology:
The channels are encoded by five genes: ASIC1 - ASIC5. ASIC1a, ASIC1b, ASIC2a, ASIC2b are splice variants. Each subunit has 2 transmembrane domains flanking a large extracellular loop with short intracellular N and C termini. Three of these protein subunits assemble to form the ASIC ion channel, which can combine into both homotrimeric and heterotrimeric channels.
Regulation and function:
Neuronal voltage-insensitive cationic channels activated by extracellular protons. ASICs are Na+ permeable with ASIC1a showing low Ca2+ permeability. The role of the ASIC is to sense reduced levels of extracellular pH and result in a response or signal from the neuron.
ASIC1a: Background information
ASIC1a functions as proton-gated sodium channel which is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Three isoforms have been described for the human acid-sensing ion channel 1: Isoform 2 (ASIC1a) and isoform 3 (ASIC1b) function as proton-gated sodium channels, Isoform 1 does not display proton-gated cation channel activity. ASIC1a has a high selectivity for sodium ions and can also transport lithium ions with high efficiency. Furthermore, it can also transport potassium, but with lower efficiency.
Primarily expressed in central and peripheral neurons.
Functions as a postsynaptic proton receptor that influences intracellular Ca2+ concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines.
Frozen shoulder, panic disorder, autoimmune optic neuritis, pseudohypoaldosteronism, type i
Homotrimer or heterotrimer with other ASIC proteins, in particular ASIC2, ASIC1b
STOM (Erythrocyte band 7 integral membrane protein) regulates channel activity. Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel. Phosphorylation by PKC may regulate the channel.
Ibuprofen, amiloride, diminazene, cesium, spider venom psalmotoxin-1, snake venom mambalgin-1
Patch Clamp: whole cell, room temperature, pH activation
Reviews and Links
- Lingueglia E. & Lazdunski M., Pharmacology of ASIC channels (2013) Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 2:155–171. doi: 10.1002/wmts.88
- Deval E. et al., Acid-sensing ion channels (ASICs): pharmacology and implication in pain. (2010) Pharmacology & Therapeutics 128:549–558
- Wemmie J.A. et al., Acid-sensing ion channels in pain and disease. (2013) Nature Reviews Neuroscience 14(7):461-471. doi: 10.1038/nrn3529
Transporter classification database: