Differential effects of trimethylamine and quinine on seizures induced by 4-aminopyridine administration in the entorhinal cortex of vigilant rats.
In vivo and in vitro evidence from animals suggesting that gap junctions (GJs) play a role in the spreading of epileptiform activity. We have examined the influence of the gap junction opener trimethylamine (TMA) and the connexin 36 (Cx36) gap junctional blocker, quinine, on epileptiform activity induced by 4-aminopyridine (4-AP) in the rat entorhinal cortex (EC) and the CA1 hippocampal region. A cannula and surface electrodes were implanted into the brain to administer drugs and to monitor electrical activity. Injection of 4-AP (10 nmol) produced epileptiform discharge trains of high amplitude and frequency associated with seizure behavior rated between 0 and 3 in the Racine scale. In the presence of TMA (500 nmol), 4-AP produced distinct epileptiform patterns with continuous, long epileptiform discharges of high amplitude and frequency associated with seizure behavior of 0, 1, 3 and 5 during the first 30 min post-drug administration that diminished after 90 min. Quinine injection (35 pmol) into the EC of seizing animals decreased the amplitude and frequency of the discharge trains in the EC and CA1 regions, which were completely blocked after 34 min. Indeed, the seizure behavior of the animals was completely blocked in five of the six rats 53.2s after quinine administration. We suggest that the intensity of the proepileptic effect of TMA on epileptiform activity depends on the time and route of drug administration, and that neural Cx36-dependent GJs are important structures in the generation of epileptiform activity, as well as in the seizure behavior induced by 4-AP.
Medina-Ceja
Laura
L
Department of Cellular and Molecular Biology, University of Guadalajara, 45110 Guadalajara, Jalisco, Mexico. lmedina@cucba.udg.mx
Ventura-Mejía
Consuelo
C
D015761:4-Aminopyridine; D000818:Animals; D001386:Azides; D001522:Behavior, Animal / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000187:drug effects* / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017629:Gap Junctions / Q000187:drug effects*; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D015282:Octreotide / Q000031:analogs & derivatives; D026902:Potassium Channel Blockers; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014851:Wakefulness
D001386:Azides; D008744:Methylamines; D026902:Potassium Channel Blockers; C074329:EE 581; D011803:Quinine; D015761:4-Aminopyridine; C023336:trimethylamine; D015282:Octreotide