The downregulation of Kv1 channels in Lgi1 mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Neurobiology of Disease Année : 2024

The downregulation of Kv1 channels in Lgi1 mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels

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In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 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 Kv1 remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 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 Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.
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inserm-04572150 , version 1 (10-05-2024)

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Jorge Ramirez-Franco, Kévin Debreux, Marion Sangiardi, Maya Belghazi, Yujin Kim, et al.. The downregulation of Kv1 channels in Lgi1 mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels. Neurobiology of Disease, 2024, 196, pp.106513. ⟨10.1016/j.nbd.2024.106513⟩. ⟨inserm-04572150⟩
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