Glutamate mediates most of the excitatory transmission in the brain, and AMPA receptors are the primary synaptic receptors for the fast excitatory transmission. The receptors were named after the synthetic agonist, α-amino-3-hydroxy-5-methyl-4-isoxazo1e-4-propionate (AMPA), which elicits a relatively selective activation of members of this subfamily of glutamate receptors (GluRs). AMPA-induced activation of the receptor initiates a current comprised of a fast-desensitizing component and a steady-state component. Most excitatory synapses contain both AMPA and N-methyl-D-aspartate (NMDA) receptors, and synaptically released glutamate elicits a two-component excitatory postsynaptic current (EPSC). The component with rapid onset and decay is mediated by AMPA receptors, whereas the component with a slow rise time and delayed decay involves NMDA receptors. Rapid desensitization of AMPA receptors controls the time course of EPSC at many synapses. This chapter discusses the molecular structure, properties, and regulation of AMPA receptors, along with their distribution, pharmacology, and therapeutic applications.
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