ASIC1a | acid-sensing Ion Channel 1 Isoform 2

Family:
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

Overview:

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.

Data Sheet:

Gene:
ASIC1

Human Protein:
UniProt P78348

Tissue:
Primarily expressed in central and peripheral neurons.

Function/ Application:
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.

Pathology:
Frozen shoulder, panic disorder, autoimmune optic neuritis, pseudohypoaldosteronism, type i

Accessory subunits:
Homotrimer or heterotrimer with other ASIC proteins, in particular ASIC2, ASIC1b

Interaction:
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.

Modulator:
Ibuprofen, amiloride, diminazene, cesium, spider venom psalmotoxin-1, snake venom mambalgin-1

Assays:
Patch Clamp: whole cell, room temperature, pH activation

Reviews and Links

Recommended Reviews:

Application Notes

hASIC1a - "Pharmacology of human ASIC1a channels on Nanion’s SyncroPatch 384i"

SyncroPatch 384i (a predecessor model of the SyncroPatch 384) application note: (1.4 MB)
Cells were kindly provided by Charles River.

preview the file here for download

Publications

2020 - Mechanism and site of action of big dynorphin on ASIC1a

SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Publication in PNAS (2020)

Authors:
Borg C.B., Braun N., Heusser S.A., Bay Y., Weis D., Galleano I., Lund C., Tian W., Haugaard-Kedström L.M., Bennett E.P., Lynagh T., Strømgaard K., Andersen J., Pless S.A.

2021 - High-Throughput Screening of TRPV1 Ligands in the Light of the Bioluminescence Resonance Energy Transfer Technique

SyncroPatch 384 Publication in Molecular Pharmacology (2021)

Authors:
Chappe Y., Michel P., Joushomme A., Barbeau S., Pierredon S., Baron L., Garenne A., Poulletier De Gannes F., Hurtier A., Mayer S., Lagroye I., Quignard J-F., Ducret T., Compan V., Franchet C., Percherancier Y.

2022 - The suitability of high throughput automated patch clamp for physiological applications

SyncroPatch 384 Publication in The Journal of Physiology (2022)

Authors:
Obergrussberger A., Rinke-Weiß I., Goetze T.A., Rapedius M., Brinkwirth N., Becker N., Rotordam M.G., Hutchison L., Madau P, Pau D, Dalrymple D., Braun N., Friis S., Pless S.A., Fertig N.

hASIC1a