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Title

Involvement of calmodulin-dependent protein kinase II in carbachol-induced rhythmic activity in the hippocampus of the rat

Authors
Boeijinga, P. H.
Boddeke, H. W.
Published in Brain Research. 2000, vol. 872, no. 1-2, p. 11-19
Abstract The role of calcium and protein kinases in rhythmic activity induced by muscarinic receptor activation in the CA1 area in rat hippocampal slices was investigated. Extracellular recording showed that carbachol (20 microM) induced synchronized field potential activity with a dominant frequency of 7.39+/-0.68 Hz. Pretreatment with the membrane permeable Ca(2+) chelator BAPTA-AM (50 microM) or with thapsigargin (1 microM), a compound which depletes intracellular calcium stores, reduced the dominant power of carbachol-induced theta-like activity by 83% and 78%, respectively. Inhibition of calmodulin-dependent protein kinase II (CaMKII) by the cell permeable inhibitor KN-93 (10 microM) reduced the power of carbachol-induced theta-like activity by 80%. In contrast the protein kinase C (PKC) inhibitor calphostin C did not significantly (P>0.05) affect the effect of carbachol. Whole-cell recording indicated that KN-93 also blocked carbachol-induced suppression of slow I(AHP) and strongly inhibited the carbachol-induced plateau potential. Our data suggest that activation of CaMKII by carbachol is crucial for local theta-like activity in the CA1 area of the rat hippocampus in vitro. Furthermore, involvement of CaMKII in carbachol-induced suppression of the slow I(AHP) and the induction of plateau potentials could play a role in the induction of theta-like rhythmic activity by carbachol.
Keywords AnimalsBenzylamines/pharmacologyCalcium/metabolismCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/ metabolismCarbachol/ pharmacologyCell Membrane/drug effects/metabolismCholinergic Agonists/pharmacologyEgtazic Acid/ analogs & derivativesEnzyme Inhibitors/pharmacologyHippocampus/cytology/ drug effects/ enzymologyMaleMembrane Potentials/drug effectsMuscarinic Agonists/pharmacologyMuscarinic Antagonists/pharmacologyPatch-Clamp TechniquesPeriodicityPotassium/metabolismProtein Kinase C/metabolismPyramidal Cells/drug effects/metabolismRatsRats, Sprague-DawleySecond Messenger Systems/drug effectsSulfonamides/pharmacologyTheta Rhythm/drug effects
Stable URL http://archive-ouverte.unige.ch/unige:10156
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PMID: 10924670
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