The role of Ca2+/calmodulin-dependent protein kinase II in mechanisms underlying neuronal hyperexcitability induced by repeated, brief exposure to hypoxia or high K+ in rat hippocampal slices

Abstract

Analysis of extracellular recordings of evoked excitatory postsynaptic potentials and population spikes from rat hippocampal slices has previously revealed that repeated, brief exposures to high extracellular K(+) or to episodes of hypoxia induce a sustained (more than 3 h) hyperexcitability of CA1 pyramidal neurons accompanied with epileptiform activity which was dependent on activation of L-type Ca(2+) channels and N-methyl-D-aspartate receptors. Using in vitro phosphorylation assay we have found the significant increase of Ca(2+)-independent activity of Ca(2+)/calmodulin-dependent protein kinase II in CA1 region of hippocampal slices 60 min after the high extracellular K(+) and 60-80 min after the hypoxic episodes. These data suggest possible involvement of Ca(2+)/calmodulin-dependent protein kinase II in Ca(2+)-dependent mechanisms of the maintenance phase of the observed epileptiform activity.