Ca2+–Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration

Neurological diseases, including global ischemia, Alzheimer's disease and amyotrophic lateral sclerosis, are characterized by selective patterns of neurodegeneration. Most studies of potential glutamate-receptor-mediated contributions to disease have focused on the highly Ca2+-permeable and widely distributed NMDA-receptor channel. However, an alternative hypothesis is that the presence of AMPA- or kainate-receptor channels that are directly permeable to Ca2+ ions (Ca-A/K-receptor channels) is of greater significance to the neuronal loss seen in these conditions. Besides a restricted distribution and high Ca2+ permeability, two other factors make Ca-A/K receptors appealing candidate contributors to selective injury: their high permeability to Zn2+ ions and the possibility that their numbers increase in disease-associated conditions. Further characterization of the functions of these channels should result in new approaches to treatment of these conditions.