Figure 2.

Ion channel dysregulations that contribute to cortical hyperexcitability in Fmr1 KO neurons. (A) Fmr1 KO dendrites present with altered composition of ion channels when measured with electrophysiological and immunofluorescence measures. Increased I-K_A currents (potentially mediated by Kv4.2 channels) can support faster firing of dendritic action potentials. Reduced HCN currents (likely through HCN1 channels) reduce dendritic hyperpolarization, thus disinhibiting dendritic action potential firing. (B) Fmr1 KO axons display increased currents through persistent and fast Na⁺ channels, both of which are associated with neuronal hyperexcitability. The increase in Na⁺ currents is combined with reduced delayed rectifier K⁺ currents, further enhancing a hyperexcitable state of the Fmr1 KO axon.