K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons

Abstract

Pyramidal neurons receive tens of thousands of synaptic inputs on their dendrites. The dendrites dynamically alter the strengths of these synapses and coordinate them to produce an output in ways that are not well understood. Surprisingly, there turns out to be a very high density of transient A-type potassium ion channels in dendrites of hippocampal CA1 pyramidal neurons. These channels prevent initiation of an action potential in the dendrites, limit the back-propagation of action potentials into the dendrites, and reduce excitatory synaptic events. The channels act to prevent large, rapid dendritic depolarizations, thereby regulating orthograde and retrograde propagation of dendritic potentials.

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

“…The density of I A channels in CA1 dendrites increases with distance from the soma [16] . Moreover, in distal dendrites, these channels increase the probability of channel opening at the resting membrane potential due to their hyperpolarization-shifted conductance of the inactivation curve during synaptic LTP [21] .…”

“…Moreover, in distal dendrites, these channels increase the probability of channel opening at the resting membrane potential due to their hyperpolarization-shifted conductance of the inactivation curve during synaptic LTP [21] . Blocking I A channels in dendrites with 4-aminopyridine enhances the back-propagation of dendritic APs and boosts EPSPs [16] .…”

“…Interestingly, it has been reported that dendritic I A channels actively shape synaptic inputs and that the pharmacological blockade of I A channels strongly enhances the amplitude and summation of EPSPs [16,18] .…”

“…This local Ca 2+ infl ux requires postsynaptic depolarization as well as the activation of NMDARs [21,47,48] . Because depolarization in dendritic or postsynaptic membranes is critically dependent on back-propagating APs, the high dendritic density of I A channels is considered to be a key factor in reducing the Ca 2+ influx in postsynaptic sites and dendritic shafts [16,49] .…”

“…Genetic identification in Drosophila has revealed that several channel proteins encoded by the Shal family of K + channels (Kv4 channels) underlie the major I A in the somatodendritic compartment of neurons and show a more hyperpolarized voltage-dependence of gating properties [11,12] , while Shaker channels (Kv1) are localized exclusively to muscle cells [13] . 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] .…”