Abstract
To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, we examined the effects of MTH on hippocampal CA1 and neocortical neuronsvia extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 μM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region, but enhanced γ-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic currents and induced spontaneous inhibitory postsynaptic currents in neocortical and hippocampal CA1 neurons. In addition, MTH induced a tonic, bicuculline-sensitive hyperpolarization in association with increases in membrane conductance, suggesting a direct stimulation of GABAA receptors by MTH. Spontaneous epileptiform activity was not observed in the neocortex and hippocampus after exposure of slices to MTH, neither in the standard in vitrocondition nor in the presence of 4-aminopyridine, which promotes rhythmic synaptic activities. We suggest that the activation of epileptiform activity in vivo by MTH may result from increased neuronal synchrony via the potentiation of GABAA-mediated synaptic inhibition.
Footnotes
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Send reprint requests to: Dr. R. Wennberg, Department of Medicine (Neurology), The Toronto Hospital, 399 Bathurst Street, EC8–022, Toronto, Ontario, Canada M5T 2S8. E-mail:r.wennberg{at}utoronto.ca
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↵1 This work was supported by the MRC of Canada. L. Zhang is a Scholar of the Heart and Stroke Foundation of Ontario and Canada.
- Abbreviations:
- MTH
- methohexital
- IPSC
- inhibitory postsynaptic current
- EPSP
- excitatory postsynaptic potential
- f-EPSP
- field excitatory postsynaptic potential
- CNQX
- 6-cyano-7-nitroquinoxaline-2,3-dione
- D-AP5
- d-(−)-2-amino-5-phosphonopentanoic acid
- ACSF
- artificial cerebrospinal fluid
- Received February 9, 1998.
- Accepted April 16, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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