Российская академия наук


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Serdyuk T.S.

Kogan Research Institute of neurocybernetics, Southern Federal University, Rostov-on-Don, Russia, serta@bk.ru

Gap junction plays critical role in the generation and synchronization of the neuronal activity. Recent studies claimed that gap junction are involved either normal or pathological events, i.e. epilepsy. Numerous data have been collected about presence of gap junctions in the different brain structures, particularly in the cortex, between interneurons. For example, electrical synapses synchronize activity between GABA interneurons which are formed into neuronal assembles. The aim of present study is to investigate the effects of gap junction blocker carbenoxolone on carbachol-induced experimental epilepsy. Non-linear immobilized and artificially ventilated laboratory rats were used in the present study. Local extracellular field potentials in the somatic cortical area was recorded by pairs of microelectrodes in the infragranular and supragranular layers of a single column. The experimental protocol was approved by the Bioethics Commission of the Southern Federal University. Carbenoxolone (100mcM) was used as gap junctions blocker. Carbachol (12.5 mcM) was used as convulsive agent. Microapplication of carbachol solution through microelectrode induced an epileptic EEG activity characterized by spike-wave complexes both in the infragranular and supragranular layers of a single column. Then Microapplication of carbenoxolone solution was applied in the infragranular layers of a single column. Effects of carbenoxolone on epileptic activity were assessed by electrophysiological analysis. It was found that admini-

stration of carbenoxolone decreased amplitude of the local field potentials. Amplitude of the local field potentials started to grow within 15 minutes after microapplication of carbenoxolone. After 30 minutes after microapplication of carbenoxolone amplitude of the local field potentials has reached initial level but epileptic activity still has not appeared except rare high-voltage spikes. The results of this study suggest that carbenoxolone has anticonvulsive effect on epileptic activity therefore the blockade of gap junction may contribute to the prevention of epileptic activity. It was previously shown for other gap junction blockers such as octanol, heptanol and halothane. Previously studies suggest that a structural adjustment in gap junction proteins leads to facilitation and propagation of synchronize neuronal activity. It appears that gap junction blockers are able to slow structural adjustment. It can be a possible mechanism of anticonvulsive effects of gap junction blockers. However, these mechanisms are still unknown exactly as well as mechanisms of gap junction blockers on neuronal activity in absence of increased excitability.

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