AMPA Receptors: Disease

Alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate fast synaptic transmission at excitatory synapses in the central nervous system. Proper AMPAR function and regulation are critical to neuronal development, synaptic plasticity, and structural remodeling. Excessive activation of AMPARs is thought to play a role in a number of neurological disorders and diseases. Ca²⁺ permeation through AMPARs lacking the glutamate receptor (GluR)-2 subunit is thought to play a critical role in the cell death associated with ischemia, seizure, and amyotrophic lateral sclerosis. While in many brain regions AMPARs are impermeable to calcium under physiological conditions, AMPAR subunit composition and Ca²⁺ permeability are dynamically regulated in response to neuronal insults. Recent studies now demonstrate that these changes arise, not only from activity-mediated alterations in gene expression, but also from trafficking of AMPARs, RNA editing, and local dendritic protein synthesis. This article reviews new insights into the role of Ca²⁺-permeable AMPARs in neurological diseases and disorders.