Abstract
We show that alpha and betaCaMKII are inversely regulated by activity in hippocampal neurons in culture: the alpha/beta ratio shifts toward alpha during increased activity and beta during decreased activity. The swing in ratio is approximately 5-fold and may help tune the CaMKII holoenzyme to changing intensities of Ca(2+) signaling. The regulation of CaMKII levels uses distinguishable pathways, one responsive to NMDA receptor blockade that controls alphaCaMKII alone, the other responsive to AMPA receptor blockade and involving betaCaMKII and possibly further downstream effects of betaCaMKII on alphaCaMKII. Overexpression of alphaCaMKII or betaCaMKII resulted in opposing effects on unitary synaptic strength as well as mEPSC frequency that could account in part for activity-dependent effects observed with chronic blockade of AMPA receptors. Regulation of CaMKII subunit composition may be important for both activity-dependent synaptic homeostasis and plasticity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics*
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Animals
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Calcium Signaling / drug effects
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Calcium Signaling / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cells, Cultured
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Immunohistochemistry
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Neural Pathways / cytology
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Neural Pathways / drug effects
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Neural Pathways / enzymology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / enzymology*
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Presynaptic Terminals / ultrastructure
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics*
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Tetrodotoxin / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / genetics
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gamma-Aminobutyric Acid / biosynthesis
Substances
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Excitatory Amino Acid Antagonists
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Tetrodotoxin
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gamma-Aminobutyric Acid
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases