Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy

Acid-sensing ion channels (ASICs) constitute a recently discovered family o f excitatory cation channels, structurally related to the superfamily of de generin/epithelial sodium channels. ASIC1b and ASIC3 are highly expressed i n primary sensory neurons and are thought to play a role in pain transmissi on related to acidosis. ASIC1a, ASIC2a, and ASIC2b are also distributed in the central nervous system where their function remains unclear. We investi gated here the regulation of their expression during status epilepticus (SE ), a condition in which neuronal overexcitation leads to acidosis. In anima ls treated with pilocarpine (380 mg/kg) to induce SE, we observed a marked decrease of ASlC2b mRNA levels in all hippocampal areas and of ASIC1a mRNA levels in the CA1-2 fields. These changes were also observed after protecti ve treatment from neuronal cell death with diazepam (10 mg/kg) and pentobar bital (30 mg/kg). These findings suggest a key role of channels containing ASIC1a and ASIC2b subunits in both normal and pathological activity of hipp ocampus. (C) 2001 Academic Press.