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.
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.
Yechikhov
Sergey
S
Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia. wistar@mail.ru
Shchipakina
Tatyana
T
Savina
Tatyana
T
Kalemenev
Sergey
S
Levin
Sergey
S
Godukhin
Oleg
O
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D017610:Calcium Compounds / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005110:Extracellular Space; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D017966:Pyramidal Cells / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000378:metabolism; D009435:Synaptic Transmission
D020746:Calcium Channels, L-Type; D017610:Calcium Compounds; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases