Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. 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. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 discrimates stronger than isoform 1 between monovalent cations. Isoform 3 can flux Ca(2+) while isoform 1 cannot. Heteromeric channels composed of isoform 2 and isoform 3 are active but have a lower pH-sensitivity. 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. Inhibited by the diuretic amiloride. Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM and PRKCABP (By similarity). Interacts with ASIC2. Interacts with the spider venom Pi-hexatoxin-Hi1a (PubMed:28320941). Homotrimer of Asic1a interacts with the spider venom psalmotoxin-1 (PubMed:10829030, PubMed:26248594). Homotrimer of Asic1a (isoform 1) and Asic1b (isoform 3) and heterotrimer of Asic1a/Asic1b interact with the spider venom Pi-theraphotoxin-Hm3a (PubMed:28327374). Homotrimer of Asic1a (ASIC1 isoform 1) interacts with the snake venom mambalgin-1, mambalgin-2 and mambalgin-3 (PubMed:23034652, PubMed:23624383, PubMed:24323786, PubMed:24695733, PubMed:26680001). Homotrimer of Asic1b (isoform 3) interacts with the snake venom mambalgin-1, mambalgin-2 and mambalgin-3 (PubMed:23034652, PubMed:23624383, PubMed:24323786, PubMed:26680001). Heterotrimer of Asic1a-Asic1b (ASIC1 isoform 1-ASIC1 isoform 3) interacts with the snake venom mambalgin-1 and mambalgin-2 (PubMed:23034652). Heterotrimer of Asic1a-Asic2a interacts with the snake venom mambalgin-1, mambalgin-2 and mambalgin-3 (PubMed:23034652, PubMed:23624383, PubMed:26680001). Heterotrimer of Asic1a-Asic2b (ASIC1 isoform 1-ASIC2 isoform 2) interacts with the snake venom mambalgin-1 and mambalgin-2 (PubMed:23034652). Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 (By similarity). Expressed in dorsal root ganglia and sciatic nerve (at protein level). Widely distributed throughout the brain. Expressed in olfactory bulb, neo and allocortical regions, dentate granule cells, pyramidal cells of CA1-CA3 subfields of the hippocampal formation, habenula, basolateral amygdaloid nuclei, and in the Purkinje and granule cells of the cerebellum. Diffusely detected over most other regions of the basal ganglia, including thalamic nuclei, substantia nigra, striatum and globus pallidus, hypothalamus, midbrain, pons, medulla and choroid plexus. Isoform 3 is expressed only in dorsal root ganglion (DRG) while isoform 1 is expressed in DRG, spinal chord, trigeminal ganglia and the trigeminal mesencephalic nucleus. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs. 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 (By similarity). Potentiated by Ca(2+), Mg(2+), Ba(2+), multivalent cations and potentiated by FMRFamide-related neuropeptides. pH dependence may be regulated by serine proteases. Inhibited by anti-inflammatory drugs like salicylic acid. Isoform 1 homomultimeric channel is specifically and reversibly inhibited by psalmotoxin-1, a spider venom toxin, while isoform 2 and other ASICs are insensitive. Inactive. Blocked by Ca(2+). Mutagenesis of Asp-465 to Asn reduces Ca(2+) block. Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.