ABSTRACT
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) was the –rst idiopathic epilepsy to be associated with a speci–c mutation that showed a single-gene inheritance pattern (Scheffer et al. 1995), and as such it became a model for understanding how a focal epilepsy could arise from a mutation in a widely expressed gene. The identi–ed disease-causing mutations are in the α4 or β2 subunits of the nicotinic acetylcholine receptor (nAChR), a pentameric protein complex containing a cation-selective channel that produces a brief depolarizing potential upon activation. The known disease-causing mutations are all located near the proposed ion channel pore of the receptor complex (Steinlein and Bertrand 2008) and therefore affect the function of the receptor. nAChRs also possess variable permeability to calcium ions, conferring the potential to in§uence intracellular signaling pathways or directly modulate neurotransmitter release in addition to their depolarizing effects.
