Zn(2+) permeates Ca(2+) permeable AMPA/kainate channels and triggers selective neural injury.
Brief exposures of cortical cultures to kainate (100 mu M) plus Zn(2+) (300 mu M) cause fluorescence of the Zn(2+) sensitive dye, TS-Q, to appear in virtually all neurons, probably reflecting depolarization and secondary Zn(2+) permeation through voltage-sensitive Ca(2+) channels. However, if Na+ ions are removed from the media (to prevent depolarization), prominent TS-Q fluorescence is still observed in the small subset of neurons labeled by kainate stimulated Co(2+) uptake (Co(2+)(+) neurons), a histochemical technique that identifies neurons expressing Ca(2+) permeable AMPA/kainate receptor-gated channels. Kainate/Zn(2+) exposures in Na+ containing media with lower (50-100 mu M) Zn(2+) concentrations resulted 24 h later in selective loss of the Co(2+)(+) neurons, suggesting that these channels may permit particularly high rates of Zn(2+) passage. Thus, direct permeation of synaptically released Zn(2+) through Ca(2+) permeable AMPA/kainate channels could contribute to selective degeneration of neurons in disease as well as subserving physiological signaling functions.
Yin
H Z
HZ
Department of Neurology, University of California, Irvine, 92717-4290, USA.
Weiss
J H
JH
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D009410:Nerve Degeneration; D018091:Receptors, AMPA / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D015032:Zinc