Journal article

Generalized epilepsy with febrile seizures plus-associated sodium channel beta 1 subunit mutations severely reduce beta subunit-mediated modulation of sodium channel function

R Xu, EA Thomas, EV Gazina, KL Richards, M Quick, RH Wallace, LA Harkin, SE Heron, SF Berkovic, IE Scheffer, JC Mulley, S Petrou



Two novel mutations (R85C and R85H) on the extracellular immunoglobulin-like domain of the sodium channel beta1 subunit have been identified in individuals from two families with generalized epilepsy with febrile seizures plus (GEFS+). The functional consequences of these two mutations were determined by co-expression of the human brain NaV1.2 alpha subunit with wild type or mutant beta1 subunits in human embryonic kidney (HEK)-293T cells. Patch clamp studies confirmed the regulatory role of beta1 in that relative to NaV1.2 alone the NaV1.2+beta1 currents had right-shifted voltage dependence of activation, fast and slow inactivation and reduced use dependence. In addition, the NaV1.2+beta1 c..

View full abstract