Synaptic Mechanisms of Action of Convulsion-Producing Anticholinesterases. Characterization of Di-Isopropyl Phosphorofluoridate-Induced Epileptiform Activity in the Mammalian Hippocampus.
Annual summary rept. no. 1, Sep 82-Sep 83,
BAYLOR COLL OF MEDICINE HOUSTON TX DEPT OF NEUROLOGY
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The purpose of this work was to elucidate the convulsant mechanisms of action of the irreversible organophosphorus anticholinesterase anti-ChE di-isopropyl phosphorofluoridate DFP. In these experiments pyramidal cell responses from rat and guinea-pig hippocampal slices were examined in vitro using standard extra- and intracellular microelectrode recording techniques. When bath-applied at 10-25 micrometers for 30 min, DFP produced spontaneous, rhythmic discharges 50-400 msec in duration at 0.1-0.3 Hz in the previously quiescent extracellular field recordings. This activity was superficially similar to that produced by other convulsants, e.g., bicuculline and picrotoxin, which interfere with inhibitory synaptic activity that is mediated by gamma-aminobutyric acid. This DFP-induced effect was readily abolished upon washout, even in slices that were exposed for up to 5 hrs. Reintroduction of the DFP solution reinitiated these epileptiform events. The DFP-induced events, however, were not suppressed with the cholinesterase reactivator pralidoxime 10-100 micrometer, but were abolished by high concentrations of atropine 10-100 micrometers. Other anti-ChEs tested were the carbamates neostigmine, physostigmine and pyridostigmine 10-500 micrometers.
- Anatomy and Physiology