Further characterization of two oppositely acting, epilepsy-associated mutations at position H310 of Kv1.2 (KCNA2) channels.

Abstract

KV1.2, encoded by KCNA2, is a prominent voltage-gated potassium channel that controls neuronal excitability. Two KCNA2 mutations (p.H310Y, p.H310R), within the voltage-sensing domain (VSD) have been associated with epileptic encephalopathy and intellectual disability. Last year we showed that H310Y had a double gain-of-function effect, increasing surface trafficking and slowing channel closure by ∼4-fold. Despite producing similar clinical outcomes, H310R showed a loss-of-function effect, abolishing surface trafficking. Here, we further characterize the properties of these mutations.