Abstracts

Rationale: KCNQ channels are voltage-gated potassium channels, which potently inhibit repetitive firing of action potentials. Recently, de novo mutations in KCNQ2 subunit were reported to be associated with epileptic encephalopathy, a severe symptomatic drug-resistant epilepsy with severe psychomotor retardation. Specifically, some of these mutations were found in two helical regions (A and B) in KCNQ2 C-terminal tail that interact with calmodullin (CaM). Two mutations (R333W, and A337G) lie in helix A, which mediates Ca²⁺-independent CaM binding. Two other mutations (M518V, and R532W) lie in helix B, which mediates the Ca²⁺-dependent CaM binding. However, how these mutations disrupt KCNQ channel function is unknown. We have previously shown that CaM binding to the IQ motif of helix A of KCNQ2 is critical for the transport of KCNQ2/KCNQ3 channels from the endoplasmic reticulum (ER) to the axonal surface of hippocampal neurons. Thus, we hypothesize that de novo mutations in helices A and B of KCNQ2 disrupts CaM binding and the enrichment of KCNQ2/KCNQ3 channels on the axonal surface. Methods: To test this hypothesis, we performed co-immunoprecipitation, immunostaining, and electrophysiology in primary dissociated hippocampal cultured neurons. Results: This poster will present our data on the effect of de novo KCNQ2 mutations on KCNQ channel trafficking and function, which could provide an insight into the etiology of epileptic encephalopathy. Conclusions: This poster will present our data on the effect of de novo KCNQ2 mutations on KCNQ channel trafficking and function, which could provide an insight into the etiology of epileptic encephalopathy.