CaMKII modulates sodium current in neurons from epileptic Scn2a mutant mice

Significance Epilepsy is a neurological disorder affecting approximately 1% of the world population. Mutations within genes encoding voltage-gated channels are the most frequently identified cause of monogenic epilepsies. Variable expressivity is a common feature of many epilepsies, suggesting that modifier genes make significant contributions to clinical phenotype. Here, we report an investigation of the molecular basis for strain-dependent seizure severity in the Scn2a Q54 epileptic mice. We show strain-dependent differences in pyramidal cell excitability correlate with divergent properties of voltage-gated sodium channels that could be explained by differences in calcium/calmodulin protein kinase II (CaMKII)-dependent modulation of neuronal sodium channels. These findings suggest that strain-dependent sodium channel modulation by CaMKII in Scn2a Q54 mice influences excitatory neuronal networks.