title: Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus.
abstract: BACKGROUND
  Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites.
  
  
  OBJECTIVE
  The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure.
  
  
  RESULTS
  Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization.
  
  
  CONCLUSIONS
  These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston Alcohol Research Center, 67 President Street, IOP 462 North, Charleston, SC, 29425, USA, mulholl@musc.edu.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mulholland
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Spencer
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Sven
authors.initials: S
authors.lastname: Kroener
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D051605:Kv Channel-Interacting Proteins / Q000187:drug effects* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D013569:Synapses / Q000378:metabolism
chemical_list: D051605:Kv Channel-Interacting Proteins; D051672:Shal Potassium Channels; D002118:Calcium