ASIC3 | acid-sensing Ion Channel 3
Acid-sension 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.
ASIC3: Background information
Primarily expressed in central and peripheral neurons including nociceptors where they participate in neuronal sensitivity to acidosis. Also present in taste receptor cells, photoreceptors and retinal cells, testis, lung epithelial cells, urothelial cells, adipose cells, vascular smooth muscle cells, immune cells and bone.
Somatic and visceral nociception, inflammatory pain
Ischaemic stroke, implicated in multiple sclerosis, Huntington’s disease, Parkinson’s disease and spinal cord injury
Inhibitors: Amiloride, nafamostat mesilate, A-317567, APETx2, aspirin. Potentiators: FMRFa, MitTx
Patch Clamp: whole cell, room temperature, pH activation
Stably-transfected HEK293 cell line (EMD Millipore)
WIREs Membr Transp Signal 2013, 2:155–171. doi: 10.1002/wmts.88, Lingueglia & Lazdunski; Pharmacology & Therapeutics 128 (2010) 549–558, Deval et al.; Nat Rev Neurosci. 2013, 14(7): 461–471. doi:10.1038/nrn3529, Wemmie et al.