Quinine, a blocker of neuronal cx36 channels, suppresses seizure activity in rat neocortex in vivo.
OBJECTIVE
The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the 4-aminopyridine in vivo epilepsy model.


METHODS
ECoG recording was performed on anesthetized adult rats, in which either quinine, a selective blocker of Cx36, or the broad-spectrum GJ blockers carbenoxolone and octanol were applied locally, before the induction or at already active epileptic foci.


RESULTS
The blockade of Cx36 channels by quinine before the induction of epileptiform activity slightly reduced the epileptogenesis. When quinine was applied after 25-30 repetitions of seizures, a new discharge pattern appeared with frequencies >15 Hz at the initiation of seizures. In spite of the increased number of seizures, the summated ictal activity decreased, because of the significant reduction in the duration of the seizures. The amplitudes of the seizure discharges of all the patterns decreased, with the exception of those with frequencies of 11-12 Hz. The blockade of Cx36 channels and the global blockade of the GJ channels resulted in qualitatively different modifications in ictogenesis.


CONCLUSIONS
The blockade of Cx36 channels at the already active epileptic focus has an anticonvulsive effect and modifies the manifestation of the 1- to 18-Hz seizure discharges. Our findings indicate that the GJ communication via Cx36 channels is differently involved in the synchronization of the activities of the networks generating seizure discharges with different frequencies. Additionally, we conclude that both neuronal and glial GJ communication contribute to the manifestation and propagation of seizures in the adult rat neocortex.
Gajda
Zita
Z
Department of Comparative Physiology, University of Szeged, Szeged, Hungary.
Szupera
Zoltán
Z
Blazsó
Gábor
G
Szente
Magdolna
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002229:Carbenoxolone / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D017630:Connexins / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D005260:Female; D017629:Gap Junctions / Q000187:drug effects; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D000442:Octanols / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D000097004:Gap Junction delta-2 Protein
D015761:4-Aminopyridine; D002229:Carbenoxolone; D017630:Connexins; D000442:Octanols; D011803:Quinine; D000097004:Gap Junction delta-2 Protein