CHANGES OF CA2-DEPENDENT PROTEIN-KINASE-II AFTER TRANSIENT ISCHEMIA IN GERBIL HIPPOCAMPUS( CALMODULIN)

Transient cerebral ischemia induces, besides delayed neurodegeneration in selected brain structures, a number of early responses which may m ediate ischemic injury/repair processes. Here we report that 5 min exp osure to cerebral ischemia in gerbils induces a rapid inhibition and s ubsequent translocation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). These changes were partially reversible during a 24 h post- ischemic recovery. Concomitantly the total amount of the enzyme protei n, as revealed by Western blotting (a-subunit specific), remained stab le. This is consistent with our previous hypothesis, that the mechanis m of ischemic CaMKII down-regulation involves a reversible posttransla tional modification-(auto)phosphorylation, rather than the degradation of enzyme protein. The effectiveness of known modulators of postische mic outcome in counteracting CaMKII inhibition was tested. Three of th ese drugs, namely dizocilpine (MK-801), N-nitro-L-arginine methyl este r (L-NAME) and gingkolide (BN52021), all significantly attenuated the enzyme response to ischemia, whereas an obvious diversity in the time- course of their actions implicates different mechanisms involved.