SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines.
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.
Ngo-Anh
Thu Jennifer
TJ
Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Bloodgood
Brenda L
BL
Lin
Michael
M
Sabatini
Bernardo L
BL
Maylie
James
J
Adelman
John P
JP
D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D016194:Receptors, N-Methyl-D-Aspartate; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D008274:Magnesium; D002118:Calcium