Abstract
At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is required for long-term potentiation (LTP); this is a proposed cellular mechanism underlying memory and learning. Here we show that in lateral amygdala pyramidal neurons, SK channels are also activated by calcium influx through synaptically activated NMDARs, resulting in depression of the synaptic potential. Thus, blockade of SK channels by apamin potentiates fast glutamatergic synaptic potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2-amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA. Blockade of SK channels greatly enhances LTP of cortical inputs to lateral amygdala pyramidal neurons. These results show that NMDARs and SK channels are colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amygdala / physiology*
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Animals
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Calcium / antagonists & inhibitors
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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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Chelating Agents / pharmacology
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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 / physiology
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Female
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Male
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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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Patch-Clamp Techniques
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Calcium-Activated / antagonists & inhibitors
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Potassium Channels, Calcium-Activated / metabolism*
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism
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Rats
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Rats, Wistar
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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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Small-Conductance Calcium-Activated Potassium Channels
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
Substances
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Chelating Agents
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Excitatory Amino Acid Antagonists
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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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Calcium