ASIC1

Domain

Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix (By similarity).

Function

Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.

Isoform 1 does not display proton-gated cation channel activity.

Post-translational modifications

Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel.

Sequence Similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.

Tissue Specificity

Expressed in most or all neurons.

Cellular localization

• Cell membrane
• Multi-pass membrane protein
• Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 (By similarity).

Alternative names

ACCN2, BNAC2, ASIC1, Acid-sensing ion channel 1, Brain sodium channel 2, BNaC2

Database links

swissprot:P78348 omim:602866 entrezGene:41

Other research areas

• Cardiovascular