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.
Weiss
J H
JH
Dept of Neurology, University of California, Irvine, CA 92697-4292, USA.
Sensi
S L
SL
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D002118:Calcium; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D015032:Zinc