Abstract
Small-conductance Ca(2+)-activated K(+) channels (SK channels) influence the induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner. Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca(2+) influx within individual spines. SK channels are tightly coupled to synaptically activated Ca(2+) sources, and their activity reduces the amplitude of NMDAR-dependent Ca(2+) transients. These effects are mediated by a feedback loop within the spine head; during an excitatory postsynaptic potential (EPSP), Ca(2+) influx opens SK channels that provide a local shunting current to reduce the EPSP and promote rapid Mg(2+) block of the NMDAR. Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+) signals within dendritic spines.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Apamin / pharmacology
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Cells, Cultured
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Dendritic Spines / drug effects
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Dendritic Spines / metabolism*
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Dendritic Spines / ultrastructure
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Feedback, Physiological / drug effects
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Feedback, Physiological / physiology*
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Hippocampus / cytology
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Hippocampus / physiology*
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Immunohistochemistry
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Magnesium / metabolism
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Mice
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Mice, Inbred C57BL
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Organ Culture Techniques
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Calcium-Activated / drug effects
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Potassium Channels, Calcium-Activated / metabolism*
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Small-Conductance Calcium-Activated Potassium Channels
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Potassium Channel Blockers
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Potassium Channels, Calcium-Activated
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Receptors, N-Methyl-D-Aspartate
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Small-Conductance Calcium-Activated Potassium Channels
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Apamin
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Magnesium
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Calcium