The Ketogenic Diet and Potassium Channel Function

The overall objective of this Discovery Award was to explore the hypothesis the ketogenic diet KD regulates neuronal excitability by influencing potassium channel activity via the auxiliary potassium channel subunit Kv2. To test this hypothesis we have examining the impact of the ketogenic diet on mice in which the gene that encodes Kv2 has been deleted Kv2 KO mice using an in vitro model of seizure induction in which we recorded from three interconnected brain regions the hippocampus, entorhinal cortex and amygdala. Our main findings are 1 acute treatment in vitro with ketones significantly reduces epileptiform activity in the hippocampus from WT mice but not in the Kv2 KO mice 2 this effect is not observed in ex vivo slice prepared from mice maintained on the KD 3 the KD appears to increase excitability as measured by the inter-ictal interval in the entorhinal cortex and amygdala 4 deletion of Kv2 itself has a differential impact on bursting activity in the amygdala in untreated mice and this observation is not reversed by the KD which to some extent supports our initial hypothesis.