Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.
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.
Chen
Xixi
X
Center for Learning and Memory, University of Texas at Austin, Austin, Texas 78712, USA.
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
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
D051672:Shal Potassium Channels; D002118:Calcium