Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons

J Neurosci. 2006 Nov 22;26(47):12143-51. doi: 10.1523/JNEUROSCI.2667-06.2006.

Abstract

Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Blotting, Western / methods
  • Calcium / metabolism
  • Dendrites / physiology*
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology*
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Patch-Clamp Techniques / methods
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Shal Potassium Channels / deficiency
  • Shal Potassium Channels / physiology*
  • Spinal Cord / metabolism

Substances

  • Shal Potassium Channels
  • Calcium