AMPA receptor-mediated neurotoxicity: role of Ca2+ and desensitization.

Glutamate-induced neurodegeneration is the result of excessive stimulation of the different subtypes of glutamate receptors. With regard to the AMPA ((RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate) receptors it has been clear from numerous studies that in addition to the Ca2+ permeability of the receptor complexes, their desensitization properties may play a determining role in the neurodegeneration mediated by this subtype of the glutamate receptors. Recent studies have revealed important amino acid residues in the AMPA receptor subunits that control the desensitization kinetics and that may constitute important targets for drugs that may alter the desensitization of the AMPA receptor complexes.