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

The role of calcium and protein kinases in rhythmic activity induced by mus carinic receptor activation in the CA1 area in rat hippocampal slices was i nvestigated. Extracellular recording showed that carbachol (20 mu M) induce d synchronized field potential activity with a dominant frequency of 7.39+/ -0.68 Hz. Pretreatment with the membrane permeable Ca2+ chelator BAPTA-AM ( 50 mu M) or with thapsigargin (1 mu M), a compound which depletes intracell ular calcium stores, reduced the dominant power of carbachol-induced theta- like activity by 83% and 78%, respectively. Inhibition of calmodulin-depend ent protein kinase II (CaMKII) by the cell permeable inhibitor KN-93 (10 mu M) reduced the power of carbachol-induced theta-like activity by 80%. In c ontrast the protein kinase C (PKC) inhibitor calphostin C did not significa ntly (P>0.05) affect the effect of carbachol. Whole-cell recording indicate d that KN-93 also blocked carbachol-induced suppression of slow I-AHP and s trongly inhibited the carbachol-induced plateau potential. Our data suggest that activation of CaMKII by carbachol is crucial for local theta-like act ivity in the CA1 area of the rat hippocampus in vitro. Furthermore, involve ment of CaMKII in carbachol-induced suppression of the slow I-AHP and the i nduction of plateau potentials could play a role in the induction of theta- like rhythmic activity by carbachol. (C) 2000 Elsevier Science B.V. All rig hts reserved.