Abstracts

Rationale: The underlying mechanisms behind drug resistance in temporal lobe epilepsy (TLE) remain unclear. We studied the cellular response to carbamazepine in resected temporal lobe cortical tissue from patients with TLE. Methods: 350? slices of tissue were obtained from human and non-epileptic rat temporal lobe cortex. Voltage gated currents and excitability were monitored using whole-cell patch clamping standard protocols. Firing pattern analysis was done at the injected current level that produced reliable repetitive firing before and after perfusion with carbamazepine 50?M . Biocytin 0.2% was then injected through the electrode in order to assess cell morphology and location using confocal microscopy. Results: Carbamazepine suppressed high frequency neuron firing after current injection in both rat and human. All cells tested from non-epileptic rat brain slices (n=20) were sensitive to carbamazepine perfusion. Carbamazepine also suppressed firing in 10 of 14 human neurons but in 4 it had no effect. Morphological reconstruction of the patch-clamped cells in the rat revealed 9 pyramidal neurons and 11 interneurons. In the human cortex, 6 were pyramidal neurons and 8 were interneurons. The 4 cells that did not respond to carbamazepine were all interneurons. Conclusions: Drug resistance to carbamazepine in TLE may relate to a failure to suppress high frequency activity of inhibitory interneurons.