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Downregulation of the silent potassium channel Kv8.1 increases ALS motor neuron vulnerability

Huang, X.; Lee, S.; Kawaguchi, R.; Wiskow, O.; Ghosh, S.; Frost, D.; Perrault, L.; Pandey, R.; Chen, K.; Klim, J. R.; Boivin, B.; Hermawan, C.; Livak, K. J.; Geschwind, D.; Wainger, B. J.; Eggan, K.; Bean, B. P.; Woolf, C.

2023-05-08 neuroscience
10.1101/2023.05.07.539778 bioRxiv
Show abstract

The Kv8.1 potassium ion channel encoded by the KCNV1 gene is a "silent" subunit whose biological function is unknown. In ALS patient-derived motor neurons carrying SOD1(A4V) and C9orf72 mutations, its expression is highly reduced, yielding increased vulnerability to cell death without a change in motor neuronal firing. Our data suggests that Kv8.1 modulates Kv2 channel function to impact neuronal metabolism and lipid/protein transport pathways, but not excitability.

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