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. 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. Inhibited by the diuretic amiloride. Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with PRKCABP and ASIC2 (By similarity). Interacts with STOM (PubMed:15471860). Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4. Expressed in brain areas receiving strong excitatory corticofugal input. In hippocampus, expressed in the hilus of the dentate gyrus. In the cerebral cortex expressed in anterior and posterior cingulate cortex, sensory and motor cortices. In the sensory cortex strongest expression is detected in the whisker barrel field. In sensorimotor and cingulate cortex expression is elevated in layer III. Also expressed in basal ganglia, striatum, ventral pallidum, olfactory tubercle, and nucleus accumbens. Weakly expressed in thalamus with the exception of the habenula and the medial septal nuclei. In olfactory bulb, preferentially expressed in the glomerular layer, within glomeruli. Expressed in cerebellum in the molecular and granule cell layers. Strongly expressed in amygdala complex, particularly in the lateral and basolateral nuclei. Isoform 1 is more abundant in brain compared to isoform 2 (at protein level). Expressed in the nodose ganglion and dorsal root ganglion. Expressed in dendritic spine cells. 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). Mice display reduced spatial learning and memory capability, associated with absence of proton-gated currents in hippocampal neurons and impairment of hippocampal long term potentiation (LTP). They also show an increased mechanosensitivity of colonic and gastroesophageal mechanoreceptors and prolonged gastric emptying and an altered fear conditioning. 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 (By similarity). Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.