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. Inhibited by the diuretic amiloride. Inhibited by Cs(1+) ions. Inhibited by spider venom psalmotoxin-1; this locks the channel into its desensitized conformation. Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM and ASIC2 (By similarity). Interacts with PRKCABP. Homotrimer of Asic1a (ASIC1 isoform 2) interacts with spider venom psalmotoxin-1 (PubMed:19654327, PubMed:22760635). Homotrimer of Asic1a (ASIC1 isoform 2) and Asic1b (ASIC1 isoform 3) interacts with the spider venom pi-theraphotoxin-Hm3a (PubMed:28327374). Homotrimer of Asic1a (ASIC1 isoform 2) interacts with the snake venom mambalgin-1 (PubMed:23034652). Heterotrimer of Asic1a-Asic2a (ASIC1 isoform 2-ASIC2 isoform 1) interacts with the snake venom mambalgin-1 (PubMed:23034652). Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 (By similarity). Expressed in most or all neurons. 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). Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel. Potentiated by Ca(2+), Mg(2+), Ba(2+) and multivalent cations. Inhibited by anti-inflammatory drugs like salicylic acid (By similarity). Potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases. Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.