Deletion ofKv4.2Gene 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).

De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders

“…Given the property of relatively rapid recovery of Kv4 channels from inactivation at low membrane voltage levels,28 we further examined whether or not the Kv4‐mediated component of I A was specifically enhanced in P212Q‐expressing neuron by applying double voltage pulses at an interval of 100 msec 29. Here we roughly estimated I A as the initial rapidly activating and inactivating component of the current evoked by a voltage pulse to −10 mV (Fig.…”

“…The CaMKII activity was reported to enhance the surface expression level of Kv4.2 without affecting its biophysical properties 19. Kv4.2 is the major I A ‐generating channel, especially in the dendrites of hippocampal CA1 pyramidal neurons 29. The dendritic I A limits AP backpropagation into dendrites, thereby restricting postsynaptic depolarization required for the long‐term potentiation of excitatory synapses 29, 33.…”

Roles of somatic A-type K+ channels in the synaptic plasticity of hippocampal neurons

“…Genetic and molecular techniques to manipulate functional Kv4.2 activity have provided direct evidence for Kv4.2 as the molecular identity of I A channels in CA1 dendrites, and this has been further clarified electrophysiologically in in-vitro systems [17,20,43] .…”

“…Furthermore, the distribution and gating property of I A channels in dendrites influences the intracellular Ca 2+ levels in dendritic branches, as demonstrated by changes in dendritic Ca 2+ infl ux during AP back-propagation by the genetic down-or upregulation of Kv4.2 [20] . Because NMDAdependent synaptic plasticity requires Ca 2+ influx through dendritic NMDARs, the regulatory effects of I A channels (i.e.…”

“…For a decade, the Kv subunits contributing to I A in neurons have been the focus to explain the functions that modulate dendritic signal processing, AP propagation, synaptic integration, and the filtering of fast synaptic potentials [14][15][16][17][18][19] . In particular, the NMDA-dependent synaptic LTP in hippocampal neurons regulates the distribution of I A channels in spines and dendrites, indicating the existence of dynamic and active functions of these channels [2,[20][21][22][23][24] . In addition, I A channels actively alter the dendritic Ca 2+ influx during AP backpropagation for dendritic processing in hippocampal pyramidal neurons, indicating that the regulation of backpropagation may be involved in intracellular Ca 2+ signaling cascades and in the dendritic transmission of synaptic inputs [20][21][22] .…”