Influence of the TARP γ8-Selective Negative Allosteric Modulator JNJ-55511118 on AMPA Receptor Gating and Channel Conductance.

ABSTRACT: AMPA-type gultamate receptors (AMPARs) mediate excitatory signaling in the brain and are therapeutic targets for the treatment of diverse neurological disorders. The receptors interact with a variety of auxiliary subunits, including the transmembrane AMPAR regulatory proteins (TARPs). The TARPs influence AMPAR biosynthesis and trafficking and enhance receptor responses by slowing desensitization and deactivation and increasing single-channel conductance. TARP γ8 has an expression pattern that is distinct from that of other TARPs, being enriched in the hippocampus. Recently, several compounds have been identified that selectivity inhibit γ8-containing AMPARs. One such inhibitor, JNJ-55511118, has shown considerable promise for the treatment of epilepsy. However, key details of

SUBMITTER: Coombs ID 

PROVIDER: S-EPMC7615793 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature