Differential influence of non-synaptic mechanisms in two in vitro models of epileptic field bursts.

Non-synaptic interactions are known to promote epileptiform activity through mechanisms that have primarily been studied in one particular in vitro model (low Ca(2+) model). Here we characterize another non-synaptic model, where ictal-like field bursts are induced in the CA1 area of rat hippocampal slices by exposure to Cs(+) (4-5mM) together with blockers of fast chemical synaptic transmission, and compare it with the low Ca(2+) model. The Cs-induced field bursts were blocked by 1 microM tetrodotoxin, but persisted in the presence of 200 microM Cd(2+) or 300 microM Ni(2+). Hyperosmotic condition (addition of 30 mM sucrose), reduced burst amplitude, but, unlike field bursts induced by 0mM Ca(2+)/5.25 mM K(+), sucrose had no effect on frequency or duration. Intracellular alkalinization-acidification sequence induced by NH(4)Cl potentiated and blocked, respectively, the field bursts. Octanol (100-250 microM) blocked all activity in most experiments. A quantitative comparison of three gap junction antagonists (carbenoxolone (100 microM), quinidine (100-250 microM), and endothelin-3 (1-2 microM)) indicated that gap junction communication is implicated in both models. However, endothelin-3 had selective effect on the low Ca(2+)-induced field burst. The data suggest that extracellular space-dependent processes, including field effects, significantly contribute to ongoing field burst activity, whereas initiation of a field burst can occur with or without the aid of such interactions, depending on the level of neuronal excitability. Gap junctions seem to have a general role in initiating field bursts. However, the contribution to this effect from neuronal versus glial connexin types differs in the two epileptic models studied.