Trimethylolpropane phosphate induces epileptiform discharges in the CA1 region of the rat hippocampus.
The actions of trimethylolpropane phosphate (TMPP), an ethyl bicyclophosphate convulsant produced during the partial pyrolysis of some phosphate ester-based lubricants, were tested on CA1 neurons of rat hippocampal slices using intracellular recording techniques. Bath application of TMPP (0.1-100 microM) induced spontaneous paroxysmal depolarizing shifts and the associated spontaneous epileptiform bursts followed by after-hyperpolarizations in 63% of neurons tested. The TMPP-induced epileptiform bursts were blocked by muscimol, a gamma-aminobutyric acid A (GABA(A)) receptor agonist, diazepam (DZP), a GABA(A)-benzodiazepine ionophore complex agonist, or baclofen, a GABA(B) receptor agonist. While bath application of muscimol, DZP, or baclofen suppressed spontaneous activity in CA1 neurons not previously exposed to TMPP, subsequent application of TMPP (10 microM) reversed the actions of muscimol and diazepam, but not baclofen. TMPP (0.1-100 microM) also induced membrane hyperpolarization associated with an increase in peak input resistance and inward rectification in 33% of neurons tested or membrane depolarization associated with an increase in input resistance in 17% of neurons tested. In summary, TMPP induced epileptiform activities in hippocampal CA1 neurons. The epileptogenic effects of TMPP are consistent with its interaction with GABA(A)-benzodiazepine receptors.
Lin
J
J
ManTech Environmental Technology, Inc., Dayton, Ohio 45437-0009, USA.
Ritchie
G D
GD
Stenger
D A
DA
Nordholm
A F
AF
Pancrazio
J J
JJ
Rossi
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D017097:Electric Impedance; D004827:Epilepsy / Q000139:chemically induced*; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; C065518:4-ethyl-1-phospha-2,6,7 trioxabicyclo(2.2.2)octane-1-oxide; D009118:Muscimol; D001418:Baclofen; D003975:Diazepam