Tetanic Stimulation Leads to Increased Accumulation of Ca^(2+)/Calmodulin-Dependent Protein Kinase II via Dendritic Protein Synthesis in Hippocampal Neurons
mRNA for the ɑ-subunit of CaMKII is abundant in dendrites of neurons in the forebrain (Steward, 1997). Here we show that tetanic stimulation of the Schaffer collateral pathway causes an increase in the concentration of ɑ-CaMKII in the dendrites of postsynaptic neurons. The increase is blocked by anisomycin and is detected by both quantitative immunoblot and semiquantitative immunocytochemistry. The increase in dendritic ɑ-CaMKII can be measured 100-200 µm away from the neuronal cell bodies as early as 5 min after a tetanus. Transport mechanisms for macromolecules from neuronal cell bodies are not fast enough to account for this rapid increase in distal portions of the dendrites. Therefore, we conclude that dendritic protein synthesis must produce a portion of the newly accumulated CaMKII. The increase in concentration of dendritic CaMKII after tetanus, together with the previously demonstrated increase in autophosphorylated CaMKII (Ouyang et al., 1997), will produce a prolonged increase in steady-state kinase activity in the dendrites, potentially influencing mechanisms of synaptic plasticity that are controlled through phosphorylation by CaMKII.
© 1999 Society for Neuroscience. Received March 10, 1999; revised July 1, 1999; accepted July 2, 1999. This work was supported by National Institutes of Health Research Service Award NS10660 (Y.O.), Grants MH49176 and NS17660 (M.B.K.) and NS32792 (E.M.S.), and grants from the Alfred P. Sloan Foundation, Beckman Foundation, John Merck Fund, and PEW Charitable Trusts (E.M.S.). We thank Dr. Scott Fraser, director of the Caltech Biological Imaging Resource Center, for valuable technical advice and for use of the confocal microscope.
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