Amygdala kindling is a valuable model for the study of temporal lobe epilepsy in animals. The molecular mechanisms by which kindling induces seizures are not fully understood. Neuronal voltage-gated sodium channels produce currents which, when abnormally expressed, can result in epileptiform firing patterns. In order to determine the role of altered sodium channel Nav1.6 expression in kindling epileptogenesis, we studied heterozygous Nav1.6 knockout mice and their wild type littermates with in situ hybridization, immunohistochemnistry and patch-clamp recordings. Nav1.6+/- mice required a significantly greater number of stimulations to complete kindling and showed a higher afterdischarge threshold compared to wt mice. Kindled mice showed a significant upregulation of Nav1.6 mRNA and protein in CA3 hippocampal neurons. Patch clamp recordings from dissociated CA3 pyramidal neurons revealed an increase of the persistent sodium current after kindling, which would be consistent with the biophysical properties of Nav1.6. This suggests that up-regulated Nav1.6 may contribute to enhanced excitability in kindling.