Abstract
Long-term potentiation (LTP) of synaptic strength at Schaffer collateral synapses has largely been attributed to changes in the number and biophysical properties of AMPA receptors (AMPARs). Small-conductance Ca(2+)-activated K(+) channels (SK2 channels) are functionally coupled with NMDA receptors (NMDARs) in CA1 spines such that their activity modulates the shape of excitatory postsynaptic potentials (EPSPs) and increases the threshold for induction of LTP. Here we show that LTP induction in mouse hippocampus abolishes SK2 channel activity in the potentiated synapses. This effect is due to SK2 channel internalization from the postsynaptic density (PSD) into the spine. Blocking PKA or cell dialysis with a peptide representing the C-terminal domain of SK2 that contains three known PKA phosphorylation sites blocks the internalization of SK2 channels after LTP induction. Thus the increase in AMPARs and the decrease in SK2 channels combine to produce the increased EPSP underlying LTP.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Analysis of Variance
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Animals
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Disks Large Homolog 4 Protein
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Dose-Response Relationship, Radiation
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Electric Stimulation / methods
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Excitatory Amino Acid Antagonists / pharmacology
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GABA Antagonists / pharmacology
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Guanylate Kinases
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Hippocampus / cytology*
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins / metabolism
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Long-Term Potentiation / radiation effects
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Microscopy, Immunoelectron / methods
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Nerve Fibers / physiology*
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Nerve Fibers / ultrastructure
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Patch-Clamp Techniques / methods
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Phosphinic Acids / pharmacology
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Propanolamines / pharmacology
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Pyridazines / pharmacology
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Small-Conductance Calcium-Activated Potassium Channels / metabolism*
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Small-Conductance Calcium-Activated Potassium Channels / ultrastructure
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Synapses / drug effects
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Synapses / physiology*
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Synapses / ultrastructure
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Synaptic Transmission / physiology
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Synaptic Transmission / radiation effects
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Intracellular Signaling Peptides and Proteins
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Kcnn2 protein, mouse
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Membrane Proteins
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Phosphinic Acids
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Propanolamines
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Pyridazines
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Small-Conductance Calcium-Activated Potassium Channels
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CGP 55845A
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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gabazine
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Guanylate Kinases