Molecular basis for pore blockade of human Na + channel Na v 1.2 by the μ-conotoxin KIIIA

Targeting sodium channels Voltage-gated sodium (Na v ) channels have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing and ion conductance, but function is modulated by β subunits and by natural toxins that can either act as pore blockers or gating modifiers (see the Perspective by Chowdhury and Chanda). Shen et al. present the structures of Na v 1.7 in complex with both β1 and β2 subunits and with animal toxins. Pan et al. present the structure of Na v 1.2 bound to β2 and a toxic peptide, the µ-conotoxin KIIIA. The structure shows why KIIIA is specific for Na v 1.2. These and other recently determined Na v structures provide a framework for targeted drug development. Science , this issue p. 1303 , p. 1309 ; see also p. 1278