Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the acid-sensing ion channel 1 which, when activated under the acidotic tissue conditions fo...

Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the CNS, and activation of ASIC1a homomeric channels induces neuronal death after local acidosis that accompanies cerebral ischemia. The ASIC2b s...

Acidotoxicity is common among neurological disorders, such as ischemic stroke. Traditionally, Ca(2+) influx via homomeric acid-sensing ion channel 1a (ASIC1a) was considered to be the leading cause of ischemic acidotoxicity. Here we show that extracellular protons trigger a novel form of neuronal necroptosis via ASIC1a, but independent of its ion-conducting function. We identified serine/threon...