Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo

Epilepsia. 2003 Dec;44(12):1596-600. doi: 10.1111/j.0013-9580.2003.25803.x.

Abstract

Purpose: The possible role of gap junctions in the manifestation and control of the duration of seizures was tested on the 4-aminopyridine-induced epilepsy model in rats in vivo, by using electrophysiologic, pharmacologic, and molecular biologic techniques. METHODS; In electrophysiologic experiments, the functional states of the gap junctions were manipulated with a specific blocker (carbenoxolone) or opener (trimethylamine) at the already active focus of adult, anesthetized rats, 60 min after the induction of the first seizure, which was repeated spontaneously thereafter. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was used to measure the levels of connexin (Cx) 32, 43, and 36 messenger RNAs (mRNAs) prepared from the areas of the already active primary and mirror foci.

Results: After repeated seizures, the expression levels of Cx32, Cx43, and Cx36 mRNAs at the epileptic foci were increased significantly. Blockade of the gap junctions with carbenoxolone shortened the duration of seizures and decreased the amplitude of the seizure discharges, whereas their opening with trimethylamine lengthened the duration and increased the amplitude. Secondary epileptogenesis was facilitated when the gap junctions were opened. CONCLUSIONS; Our findings support the idea that, in epileptic foci, the gap junctions are involved in the expression of rhythmic ictal discharges and in the control of the duration and propagation of the individual seizures in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine
  • Animals
  • Carbenoxolone / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology
  • Connexin 43 / genetics
  • Connexins / genetics
  • Disease Models, Animal
  • Electroencephalography / drug effects
  • Epilepsy / chemically induced
  • Epilepsy / genetics
  • Epilepsy / physiopathology*
  • Female
  • Gap Junctions / drug effects
  • Gap Junctions / physiology*
  • Gene Expression
  • Male
  • Methylamines / pharmacology
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Connexin 43
  • Connexins
  • Methylamines
  • RNA, Messenger
  • connexin 32
  • connexin 36
  • 4-Aminopyridine
  • trimethylamine
  • Carbenoxolone