Topic: Kv7.3

Kv7.2 and Kv7.3 are neuronal voltage-gated potassium channel subunits encoded by KCNQ2 and KCNQ3 genes, underlying the M-current, a slowly activating and non-inactivating current involved in neuronal excitability control. Kv7.2 mutations lead to neonatal-onset epilepsies including developmental and epileptic encephalopathies (DEE), characterized by seizures, electroencephalographic abnormalities, and developmental delay. When expressed in vitro, most Kv7.2 variants cause loss-of-function (LoF) effects. In this study, we aimed to functionally characterize a de novo KCNQ2 mutation in the pore of

Kv7.2 and Kv7.3 are voltage-gated potassium channels subunits mainly expressed in neurons where they underlie the M-current (IKM), a sub-threshold K+ current controlling action potentials generation and frequency. The Kv7.2/7.3 channel opener retigabine is an antiseizures drug used until 2017 when it was withdrawn from the market for safety reasons. Since then, no Kv7 activator is currently available for clinical use. We used a drug repurposing strategy to identify novel Kv7.2/3 activators. A library of 5600 compounds, mostly represented by clinically-approved drugs, was screened in CHO cells