Ca2+/calmodulin-dependent protein kinase II in postsynaptic densities after reversible cerebral ischemia in rats.

Compartmentalization of protein kinases and association of the enzyme with strategic cellular substrates may be important for regulating signal transduction in neurons. Cerebral ischemia produced by transient 20 min occlusion of common carotid and vertebral arteries in rats caused a dramatic (3-fold) increase in Ca2+/Calmodulin-dependent protein kinase II (CaM-KII) in the fraction enriched in postsynaptic density (PSDf), the compartment of the neuron that is involved in signal transduction. This change in compartmentalization was not reversible for up to 24 h after termination of the occlusion and was followed by reduction of CaM-KII to 50% of control content one week after the insult. The observed changes in CaM-KII content did not represent general protein redistribution in PSDf after ischemia since there were no parallel changes in PSDf actin concentration. The redistribution of CaM-KII coincided with gradual (up to 80%) reduction of its activity in PSDf as tested using specific peptide substrate and endogenous CaM-KII substrates. This work provides evidence that ischemia disturbs CaM-KII distribution and activity in PSDf and this may lead to long lasting disruption of signal transduction at the synaptic level.