Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy

Voltage-gated Na⁺ channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na⁺ channel α subunits: Na_V1.1, Na_V1.2 and Na_V1.6 during epileptogenesis (induced by kainic acid) using time points that cover the period from induction to the chronic phase of epilepsy.Na_V1.1 immunoreactivity was persistently reduced at 1 day, 3 weeks and 2 months after SE in CA1 and CA3. About 50% of the Na_V1.1-positive interneurons was lost at one day after SE in all regions investigated. In the hilus a similar reduction in NeuN-positive neurons was found, while in the CA1 and CA3 region the loss in NeuN-positive neurons only reached 15% in the chronic phase of epilepsy. This implies a stronger shift in the balance between excitation and inhibition toward excitation in the CA1 and CA3 region than in the hilus. Na_V1.2 immunoreactivity in the inner molecular layer of the dentate gyrus was lower than control at 1 day after SE. It increased at 3 weeks and 2 months after SE in the inner molecular layer and overlapped with sprouted mossy fibers. Na_V1.6 immunoreactivity in the dendritic region of CA1 and CA3 was persistently reduced at all time-points during epileptogenesis. Some astrocytes expressed Na_V1.1 and Na_V1.6 at 3 weeks after SE.Expression data alone are not sufficient to explain changes in network stability, or infer causality in epileptogenesis. These results demonstrate that hippocampal sub-regional expression of Na_V1.1, Na_V1.2 and Na_V1.6 Na⁺ channel α subunits is altered during epileptogenesis in a time and location specific way. This implies that understanding epileptogenesis has to take into account several distinct and type-specific changes in sodium channel expression.