Elevated Expression Of Acid-sensing Ion Channel3Inhibits Epilepsy Via The Activation Of Interneurons

Recent studies have indicated that acid-sensing ion channels may play asignificant role in the termination of epilepsy. In particular, acid-sensing ionchannel3(ASIC3) is expressed in the central nervous system and is mostsensitive to extracellular pH. In this study, we first detected elevated ASIC3expression patterns in the brains of temporal lobe epilepsy patients andepileptic rats. ASIC3was expressed in neurons and neurogliocytes in bothhumans and in an experimental model of epilepsy, and ASIC3wascolocalized with inhibitory GABAergic interneurons. By blocking ASIC3with its antagonist APETx2, we observed that injected APETx2shortenedthe latency to seizure and increased the incidence of generalized tonic clonicseizure compared to the control group in models of both pilocarpine-andpentylenetetrazole (PTZ)-induced seizures. Additionally, blocking ASIC3significantly decreased the frequency of action potential (AP) firing ininterneurons and pyramidal neurons. These findings suggest that elevatedlevels of ASIC3may serve as an anti-epileptic mechanism and couldrepresent a novel therapeutic strategy for epilepsy treatment.