Hippocampal Na_vβ3 expression in patients with temporal lobe epilepsy

Voltage-dependent sodium channels consist of a pore-forming alpha-subunit and regulatory beta-subunits. Alterations in these channels have been implicated in temporal lobe epilepsy (TLE) and several genetic epilepsy syndromes. Recently we identified Na_vβ3 as a TLE-regulated gene. Here we performed a detailed analysis of the hippocampal expression of Na _vβ3 in TLE patients with hippocampal sclerosis (HS) and without HS (non-HS) and compared expression with autopsy controls (ACs). Immunoblot analysis showed that Na_vβ3 levels were dramatically reduced in the hippocampus, but not in the cortex of non-HS patients when compared to HS patients. This was confirmed by immunohistochemistry showing reduced Na _vβ3 expression in all principal neurons of the hippocampus proper. Sequence analysis revealed no Na_vβ3 mutations. The functional consequences of the reduced Na_vβ3 expression in non-HS patients are unknown. Altered Na_vβ3 expression might influence microcircuitry in the hippocampus, affecting excitability and contributing to epileptogenesis in non-HS patients. Further experiments are required to elucidate these functional possibilities.