Structures of voltage-gated sodium channels: In “excitable” cells, like neurons and muscle cells, a difference in electrical potential is used to transmit signals across the cell membrane. This difference is regulated by opening or closing ion channels in the cell membrane. For example, mutations in human voltage-gated sodium (Na _v ) channels are associated with disorders such as chronic pain, epilepsy, and cardiac arrhythmia. Pan et al. report the high-resolution structure of a human Na _v channel, and Shen et al. report the structures of an insect Na _v channel bound to the toxins that cause pufferfish and shellfish poisoning in humans. Together, the structures give insight into the molecular basis of sodium ion permeation and provide a path toward structure-based drug discovery. Science , this issue p. eaau2486 , p. eaau2596

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

Navigating regulated cell excitation: Voltage-gated sodium (Na _v ) channels respond to a change in voltage potential by allowing sodium ions to move into cells, thus initiating electrical signaling. Mutations in Na _v channels cause neurological and cardiovascular disorders, making the channels important therapeutic targets. Shen et al. determined a high-resolution structure of a Na _v channel from the American cockroach by electron microscopy. The structure affords insight into voltage sensing and ion permeability and provides a foundation for understanding function and disease mechanism of Na _v and the related Ca _v ion channels. Science , this issue p. eaal4326

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

Structures of voltage-gated sodium channels: In “excitable” cells, like neurons and muscle cells, a difference in electrical potential is used to transmit signals across the cell membrane. This difference is regulated by opening or closing ion channels in the cell membrane. For example, mutations in human voltage-gated sodium (Na_v) channels are associated with disorders such as chronic pain, epilepsy, and cardiac arrhythmia. Panet al.report the high-resolution structure of a human Na_vchannel, and Shenet al.report the structures of an insect Na_vchannel bound to the toxins that cause pufferfish and shellfish poisoning in humans. Together, the structures give insight into the molecular basis of sodium ion permeation and provide a path toward structure-based drug discovery.Science, this issue p.eaau2486, p.eaau2596