SCN1A gene encodes α subunit of sodium channel Nav1.1. The α subunit contains the voltage sensors and the ion-conducting pore in homologous domains (D1 to D4). Each domain contains six α-helical transmembrane segments (S1–S6) and a pore loop connecting S5 and S6. The S4 segment is responsible for conferring the voltage-gating properties of the channel. The cytoplasmic loop that connects D2 and D3 contains a determinant conferring compartmentalization in the axonal initial segment. Mammalian sodium channels are heterotrimers, composed of a large central pore-forming glycosylated α subunit (260 kDa) and 2 auxiliary β subunits. Our recent study has demonstrated that a SCN1A mutation in the pore region of Nav1.1 caused complete loss of function, whereas a mutation with the same nature and location at Nav1.3 did not cause apparent functional reduction (DOI 10.1007/s 12035-014-8802-x), suggesting that Nav1.1 is more susceptible to impairments caused by mutations than other sodium channels. This may be one of the explanations for why SCN1A mutations are more commonly identified in epilepsy than other sodium channel genes.
Copyright ©2014 Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China
Collaborative Innovation Center for Neurogenetics and Channelopathies, Guangzhou 510260, China.