Vol. 286, Issue 3, 1177-1182, September 1998

Multiple Actions of Methohexital on Hippocampal CA1 and Cortical Neurons of Rat Brain Slices¹

Liang Zhang , Yu Zhang and Richard Wennberg

Playfair Neuroscience Unit (L.Z., Y.Z.), Toronto Hospital Research Institute; Department of Medicine (Neurology) (L.Z., R.W.), and Bloorview Epilepsy Program (L.Z., R.W.), University of Toronto, Toronto, Ontario, Canada M5T 2S8

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 neurons via 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 -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 GABA_A 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 vitro condition 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 GABA_A-mediated synaptic inhibition.