Transmembrane AMPA receptor regulatory protein gamma-8-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (TARP γ-8-AMPAR)

TARP γ-8-containing AMPA-type glutamate receptors are specialized ionotropic receptor complexes where the core AMPA receptor (AMPAR) is associated with the auxiliary subunit Transmembrane AMPA Receptor Regulatory Protein (TARP) γ-8, encoded by the CACNG8 gene (UniProt Q8WXS5). These complexes are primarily responsible for mediating fast excitatory synaptic transmission in the central nervous system, with γ-8 specifically regulating the trafficking, surface expression, and gating kinetics of the receptor (Kato et al., 2016, Nature). A defining characteristic of the γ-8 subunit is its highly enriched expression in the hippocampus compared to its sparse distribution in the cerebellum and other brain regions. This regional specificity has made the γ-8-AMPAR complex a primary target for the development of site-specific anticonvulsants, such as LY3130481 (Ceremane), which act as selective negative allosteric modulators (Maher et al., 2017, CNS Drugs). By targeting the γ-8-associated pool of receptors, these drugs aim to suppress hippocampal hyperexcitability in epilepsy patients while avoiding the global neurological side effects, such as ataxia and sedation, typically seen with non-selective AMPAR antagonists like perampanel.

Other names

CACNG8-associated AMPA receptorgamma-8-containing AMPA receptorTARP gamma-8-AMPAR complexgamma-8-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

Selective negative allosteric modulation of AMPA receptors associated with the TARP gamma-8 auxiliary subunit.