SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

Nat Neurosci. 2005 May;8(5):642-9. doi: 10.1038/nn1449. Epub 2005 Apr 24.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apamin / pharmacology
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Feedback, Physiological / drug effects
  • Feedback, Physiological / physiology*
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Immunohistochemistry
  • Magnesium / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Organ Culture Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / metabolism*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Small-Conductance Calcium-Activated Potassium Channels
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Receptors, N-Methyl-D-Aspartate
  • Small-Conductance Calcium-Activated Potassium Channels
  • Apamin
  • Magnesium
  • Calcium