The downregulation of Kv channels in Lgi1mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv channels.

In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv and Kv distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv expression levels. Moreover, we find that the downregulation of these Kv channels is associated with a marked increase in bursting patterns. Finally, mass spectrometry uncovered key modifications in the Kv interactome that highlight the epileptogenic implication of Kv downregulation in LGI1 knock-out animals.