title: Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.
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.
authors.affiliation: Center for Learning and Memory, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Xixi
authors.initials: X
authors.lastname: Chen
authors.forename: Li-Lian
authors.initials: LL
authors.lastname: Yuan
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhao
authors.forename: Shari G
authors.initials: SG
authors.lastname: Birnbaum
authors.forename: Andreas
authors.initials: A
authors.lastname: Frick
authors.forename: Wonil E
authors.initials: WE
authors.lastname: Jung
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Schwarz
authors.forename: J David
authors.initials: JD
authors.lastname: Sweatt
authors.forename: Daniel
authors.initials: D
authors.lastname: Johnston
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D051672:Shal Potassium Channels / Q000172:deficiency / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D051672:Shal Potassium Channels; D002118:Calcium