CALCIUM: A Role for Neuroprotection and Sustained Adaptation

Dissociation between elevated Ca²⁺permeability and neurotoxicity. A. GluR1_A and GluR2_B immunolabeling of hippocampal neurons sevety-two hours after exposure to GluR2_B AS-ODNs. (A). In sense strand–treated controls, GluR2_B protein expression was intense and uniform within the somata and weaker in the dendrites of single cells. (B). After GluR2_B knockdown, somatic immunolabel was highly reduced at this time. (C). In sister cultures, GluR1_A protein detection was intense within the cell body as well as proximal and distal dendritic processes indicating a rise in the GluR1:2 ratio. Ca²⁺ imaging experiments showed corresponding pharmacological rises in AMPA receptor-mediated Ca²⁺ permeability. (D). Basal Ca²⁺ levels in GluR2_B AS-ODN–treated culture. (E). Pseudocolor micrographs of basal Ca²⁺ levels in GluR2_B AS-ODN–treated culture. (F). Puff application of AMPA under the same conditions significantly increased [Ca²⁺]_i in the same neurons. B. and C. Effect of GluR2_B knockdown on L-glutamate- (B) or KA- (C) treatment on cell viability in hippocampal cultures. On day twelve, cultures were treated with GluR2_B AS-ODNs, and on days thirteen or fourteen, cultures were treated with excitotoxins. Data represent the mean ± SEM of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) mean values at 570 nm that were quantified from control and experimental hippo-campal cultures. Modified from (77, 143). Reprinted with permission.