Electrophysiological properties and carbamazepine sensitivity of epileptic human cortical neurons

There are between 20 and 30 drugs available for the treatment of seizures but despite this ~30% of the epilepsy population remains unresponsive to treatment. The underlying mechanisms behind drug resistance in temporal lobe epilepsy (TLE) have not been completely identified. The purpose of this study was to determine if distinct types of neuronal firing patterns occurring in human epileptic cortex are altered by carbamazepine (CBZ). We used whole-cell patch-clamp techniques combined with intracellular labeling to electrophysiologically and morphologically characterize neuronal populations in resected cortical tissue from patients with drug resistant epilepsy. We then determined if cells were uniformly resistant to carbamazepine or whether only a subset did not respond. Cortical spiking patterns were segregated in six main clusters: adapting high frequency cluster 1 and 2 (AHF1 and AHF2), adapting low frequency cluster 1 and 2 (ALF1 and ALF2), strongly adapting low frequency group (sALF) and one spike cluster (OS). A morphological analysis showed that some spiking patterns tend to be associated with specific neuronal morphology. OS group included only pyramidal cells while adapting high frequency groups (AHF1 &AHF2) displayed typical interneuron phenotype. Finally, we found that CBZ does not uniformly suppress neuronal activity as only ~27% of interneurons and ~40% of pyramidal cells were carbamazepine insensitive. These data indicate that in humans with DRE there is a heterogeneous CBZ insensitivity in all sub-populations of neurons.