Effect of low mg(2+) and bicuculline on cell survival in hippocampal slice cultures

Abstract

A reliable model system of epileptiform insult would facilitate investigation into the underlying biological mechanisms. Epileptiform insult was induced in hippocampal slice cultures by lowering extracellular Mg(2+), (+)-bicuculline, or (-)-bicuculline methochloride, a stable salt form of bicuculline (both forms block GABA(A) receptors). Cell death was assessed by propidium iodide uptake. Low Mg(2+) or (+)-bicuculline did not produce cell death regardless of dose or incubation period. Exposure to 100 microM (-)-bicuculline methochloride for 48 hr resulted in prominent CA1 cell death. These findings demonstrate that not all pro-epileptic drugs/ion changes used routinely for electrophysiological recording of seizure activity lead to cell death in hippocampal slice cultures and that treatment with bicuculline methochloride can be used as a reliable model for epileptiform insult.