Modulation of AMPA Receptor Gating by the Anticonvulsant Drug, Perampanel.

ABSTRACT: Postsynaptic AMPA/glutamate receptors, essential for neuronal excitability, are important targets for anticonvulsant therapy. This single channel study of the selective noncompetitive AMPA receptor antagonist, perampanel, was performed on homotetrameric GluA3 receptor-channels that open in a stepwise manner to four distinct conductance levels through independent subunit activation. Previous structural studies show that perampanel binds to four sites located within the extracellular/transmembrane boundary of closed AMPA receptor-channel subunits. We found that channels exposed to 1 or 2 μM perampanel opened mainly to the two lower conductance levels in a dose-dependent manner. Comparison of the single channel results in the structures of the full length AMPA receptor in the closed state bou

SUBMITTER: Yuan CL 

PROVIDER: S-EPMC6421588 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature