Carbenoxolone depresses spontaneous epileptiform activity in the CA1 region of rat hippocampal slices.
An important contributor to the generation of epileptiform activity is the synchronization of burst firing in a group of neurons. The aim of this study was to investigate whether gap junctions are involved in this synchrony using an in vitro model of epileptiform activity. Hippocampal slices (400 microm) were prepared from female Sprague-Dawley rats (120-170 g). The perfusion of slices with a medium containing no added magnesium and 4-aminopyridine (50 microM) resulted in the generation of spontaneous bursts of population spikes of a fast frequency along with less frequent negative-going bursts. The frequency of the bursts produced was consistent over a 3h period. Carbenoxolone (100 microM), a gap junction blocker and mineralocorticoid agonist, perfused for 75 min, reduced the frequency of both types of spontaneous burst activity. Perfusion of spironolactone (1 microM), a mineralocorticosteroid antagonist, for 15 min prior to and during carbenoxolone perfusion did not alter the ability of carbenoxolone to depress the frequency of spontaneous activity. The incubation of hippocampal slices in carbenoxolone prior to recording increased the time taken for the spontaneous activity to start on change to the zero magnesium/4-aminopyridine medium and decreased the total number of spontaneous bursts over the first 60 min period. The ability of carbenoxolone to delay induction of epileptiform activity and reduce established epileptiform activity suggests that gap junctions contribute to the synchronization of neuronal firing in this model.
Ross
F M
FM
Department of Biomedical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, AB25 2ZD, Aberdeen, UK.
Gwyn
P
P
Spanswick
D
D
Davies
S N
SN
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology*; D003864:Depression, Chemical; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists; D000442:Octanols / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000819:agonists*; D013148:Spironolactone / Q000494:pharmacology; D009435:Synaptic Transmission
D000451:Mineralocorticoid Receptor Antagonists; D000442:Octanols; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D002229:Carbenoxolone