Functional characterization of ANK2 in the regulation of cortical excitability

Abstract

Ank2fl/fl (cKO) mice) show spontaneous seizure that leads to sudden death around juvenile stages. These mice show abnormally increased firing rate and excitability in somatosensory cortical pyramidal neurons. These changes also accompany decreases in the levels of Kv7.2 and Kv7.3 voltage-gated potassium channels. Kv7.2/3 activation improves neuronal excitability and mAHP in the mutant mice. These results suggest that suppressed potassium channel activity and enhanced neuronal excitability contribute to cortical hyperactivity and seizure-induced juvenile death in Ank2-mutant mice.

ANK2 is a neuronal scaffolding protein strongly implicated in autism spectrum disorder (ASD) and epilepsy, but the underlying mechanism is unknown. Here, we report that mice with homozygous Ank2 knockout restricted to excitatory cortical and hippocampal neurons (Emx1-Cre