Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus

Neuroscience. 2008 Dec 2;157(3):566-76. doi: 10.1016/j.neuroscience.2008.09.027. Epub 2008 Sep 27.


The A-type voltage-gated potassium channels (Kv4) have been proved to play a major role as modulators of somatodendritic excitability. Recent studies indicate that neuronal hyperactivity in epilepsy is associated with changes in Kv4. However, the precise regulation of Kv4 in the development of epilepsy and its underlying mechanism remain unclear. In this study, we investigated whether the expression of the Kv4.2 channel and of its major modulator, voltage-dependent potassium channel-interacting protein (KChIP1), is altered following lithium-pilocarpine induced status epilepticus (SE) and the chronic-epilepsy phase in the rat model. We found that Kv4.2 and KChIP1 expression was transiently up-regulated following SE, whereas it was down-regulated during the chronic phase: this was most prominent in the CA1 and CA3 regions. The time-course analysis of the protein expression level showed that the peak Kv4.2 up-regulation was between 6 and 24 h after SE, whereas KChIP1 expression was increased earlier and for a shorter period. The temporospatial changes in Kv4.2 were very similar to those of its major modulator KChIP1. We compared the difference in 4-aminopyridine (4-AP)-induced intracellular calcium ([Ca(2+)]i) elevation between model and control brain slices. The results showed that the [Ca(2+)]i elevation induced by the Kv4 channel blocker 4-AP was aggravated and prolonged in the model slice after SE. The functional relevance of these changes in Ca(2+) homeostasis and Kv4.2 and KChIP1 expression may be associated with intrinsic neuronal excitability regulation and epileptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Calcium / metabolism*
  • Disease Models, Animal
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Kv Channel-Interacting Proteins / metabolism*
  • Lithium Chloride
  • Pilocarpine
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Shal Potassium Channels / metabolism*
  • Status Epilepticus / chemically induced
  • Status Epilepticus / metabolism*
  • Status Epilepticus / pathology
  • Time Factors


  • Kv Channel-Interacting Proteins
  • Potassium Channel Blockers
  • Shal Potassium Channels
  • Pilocarpine
  • 4-Aminopyridine
  • Lithium Chloride
  • Calcium