Transient cerebral ischemia decreases calcium calmodulin-dependent protein kinase II immunoreactivity, but not mRNA levels in the gerbil hippocampus

During transient cerebral ischemia, intracellular calcium increases initiating a cascade of events which leads to the delayed death of neurons located in the hippocampus. Coupled to this calcium disturbance is the rapid decrease of calcium/calmodulin kinase II (CaM kinase) activity, a protein kinase critical to neuronal functioning. The present study correlated the increased locomotor activity following ischemic insult with alterations in CaM kinase mRNA levels and immunocytochemical labeling of alpha and beta CaM kinase subunits in the hippocampus. The protective effect of hypothermia was also compared with CaM kinase mRNA levels and immunoreactivity. Levels of CaM kinase message for either alpha or beta subunits was not altered in ischemic gerbils compared to sham or hypothermic ischemic conditions. Immunoreactivity for both the alpha and beta subunits was markedly reduced in the vulnerable CA1 region of ischemic animals compared to sham controls. Gerbils that underwent the ischemic insult while hypothermic showed no decrement in staining. CaM kinase-like immunoreactivity in the ischemia-resistant CA3 sector was not altered following ischemia. These data suggest that the loss of hippocampal CaM kinase immunoreactivity observed at 24 h following ischemia is not associated with a reduction in CaM kinase mRNA levels and support the notion that the rapid decline in CaM kinase activity following ischemic insult is a result of a posttranslational modification and/or translocation of the enzyme.