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

Full 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.

Author information

Author/s: Chen, Xixi (X); Yuan, Li-Lian (LL); Zhao, Cuiping (C); Birnbaum, Shari G (SG); Frick, Andreas (A); Jung, Wonil E (WE); Schwarz, Thomas L (TL); Sweatt, J David (JD); Johnston, Daniel (D);

Affiliation: Center for Learning and Memory, University of Texas at Austin, Austin, Texas 78712, USA.

Grants: MH44754 (Agency:NIMH NIH HHS) ; MH48432 (Agency:NIMH NIH HHS) ; MH57014 (Agency:NIMH NIH HHS) ; MH70857 (Agency:NIMH NIH HHS) ; NS37444 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2006-Nov; vol 26 (issue 47) : pp 12143-51

Dates: Created 2006/11/23; Completed 2006/12/15; Revised 2007/12/03;

PMID: 17122039, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.