Effect of Low Mg²⁺ 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 Mg²⁺, (+)-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 Mg²⁺ or (+)-bicuculline did not produce cell death regardless of dose or incubation period. Exposure to 100 μM (−)-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.

KEYWORDS: :

• Cell death
• convulsant
• excitotoxicity
• magnesium
• propidium iodide