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Volume 17, Number 14,
Issue of July 15, 1997
pp. 5416-5427
Copyright ©1997 Society for Neuroscience
Visualization of the Distribution of Autophosphorylated
Calcium/Calmodulin-Dependent Protein Kinase II after Tetanic
Stimulation in the CA1 Area of the Hippocampus
Received Feb. 26, 1997; revised May 6, 1997; accepted May 7, 1997.
Yannan Ouyang1,
David Kantor1,
Kristen M. Harris2,
Erin M. Schuman1, and
Mary B. Kennedy1
1 Division of Biology, California Institute of
Technology, Pasadena, California 91125, and 2 Department of
Neuroscience, Boston Children's Hospital, Harvard Medical School,
Boston, Massachusetts 02115
Autophosphorylation of calcium/calmodulin-dependent protein kinase
II (CaMKII) at threonine-286 produces
Ca2+-independent kinase activity and has been
proposed to be involved in induction of long-term potentiation by
tetanic stimulation in the hippocampus. We have used an
immunocytochemical method to visualize and quantify the pattern of
autophosphorylation of CaMKII in hippocampal slices after tetanization
of the Schaffer collateral pathway. Thirty minutes after tetanic
stimulation, autophosphorylated CaM kinase II (P-CaMKII) is
significantly increased in area CA1 both in apical dendrites and in
pyramidal cell somas. In apical dendrites, this increase is accompanied
by an equally significant increase in staining for nonphosphorylated
CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary
to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in
the total amount of CaMKII. We suggest that tetanic stimulation of the
Schaffer collateral pathway may induce new synthesis of CaMKII
molecules in the apical dendrites, which contain mRNA encoding its
-subunit. In neuronal somas, however, tetanic stimulation appears to
result in long-lasting increases in P-CaMKII independent of an increase
in the total amount of CaMKII.
Our findings are consistent with a role for autophosphorylation of
CaMKII in the induction and/or maintenance of long-term potentiation,
but they indicate that the effects of tetanus on the kinase and its
activity are not confined to synapses and may involve induction of new
synthesis of kinase in dendrites as well as increases in the level of
autophosphorylated kinase.
Key words:
long-term potentiation;
protein phosphorylation;
synapse;
synaptic regulation;
synaptic plasticity;
immunocytochemistry;
hippocampal slices
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