Abstract found on Wiley Online Library
Voltage-gated sodium and potassium channels regulate the initiation and termination of neuronal action potentials. Gain-of-function mutations of sodium channel Scn8a and loss-of-function mutations of potassium channels Kcna1 and Kcnq2 increase neuronal activity and lead to seizure disorders. We tested the hypothesis that reducing expression of Scn8a would compensate for loss-of-function mutations of Kcna1 or Kcnq2. Scn8aexpression was reduced by administration of an antisense oligonucleotide (ASO). This treatment lengthened survival of the Kcn1a and Kcnq2 mutants, and reduced seizure frequency in the Kcnq2 mutant mice. These observations suggest that reduction of SCN8Amay be therapeutic for genetic epilepsies resulting from potassium channel mutations.