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.

doi:10.1101/2023.05.07.539778

bioRxiv · 10.1101/2023.05.07.539778

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.

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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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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. Downregulation of the silent potassium channel Kv8.1 increases ALS motor neuron vulnerability. https://doi.org/10.1101/2023.05.07.539778

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