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

Author:

Huang Xuan,Lee Seungkyu,Kawaguchi Riki,Wiskow Ole,Ghosh Sulagna,Frost Devlin,Perrault Laura,Pandey Roshan,Chen Kuchuan,Klim Joseph R.,Boivin Bruno,Hermawan Crystal,Livak Kenneth J.,Geschwind Dan,Wainger Brian J.,Eggan Kevin,Bean Bruce P.,Woolf Clifford J

Abstract

AbstractThe 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.

Publisher

Cold Spring Harbor Laboratory

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