Increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II and its endogenous substrates in the induction of long-term potentiation.
Induction of long-term potentiation in the CA1 region of hippocampal slices is associated with increased activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) (Fukunaga, K., Stoppini, L., Miyamoto, E., and Muller, D. (1993) J. Biol. Chem. 268, 7863-7867). Here we report that application of high but not low frequency stimulation to two groups of afferents in the CA1 region of 32P-labeled slices resulted in the phosphorylation of two major substrates of this enzyme, synapsin I and microtubule-associated protein 2, as well as in the autophosphorylation of CaM kinase II. Furthermore, immunoblotting analysis revealed that long term potentiation induction was associated with an increase in the amount of CaM kinase II in the same region. All these changes were prevented when high frequency stimulation was applied in the presence of the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonopentanoate. These results indicate that activation of CaM kinase II is involved in the induction of synaptic potentiation in both the postsynaptic and presynaptic regions.
Fukunaga
K
K
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
Muller
D
D
Miyamoto
E
E
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation; D046911:Macromolecular Substances; D008297:Male; D008869:Microtubule-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology; D016704:Synapsins / Q000302:isolation & purification / Q000378:metabolism*
D002147:Calmodulin; D007093:Imidazoles; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D016704:Synapsins; C031938:calmidazolium; D017871:Calcium-Calmodulin-Dependent Protein Kinases