Sodium channels

The voltage-gated sodium channel Na_V1.7 plays essential roles in pain sensation. The authors report cryo-EM structures of Na_V1.7 in complexes with three pore blockers, elucidating distinct mechanisms of action of their modulation on Na_V1.7.

Voltage-gated sodium channels mediate electrical signaling. Here, authors report the cryo-EM structure of Na_VEh from the marine plant Emiliania huxleyi, revealing an unexpected mechanism of N-type fast inactivation.

Increased late sodium current due to the disruption of voltage-gated sodium channel inactivation is a common pathogenic mechanism in different arrhythmogenic syndromes. Chakouri et al. show that fibroblast growth factor homologous factors (FHFs) modulate pathogenic late sodium current in an isoform-specific way, and leverage this observation to design and test a prototype of inhibitor peptide based on a protein domain from an inhibitory FHF isoform.

Na_X is an atypical member of the voltage-gated sodium channel family that may contribute to Na⁺ homeostasis. Here, the authors describe the structural and functional attributes of the human Na_X channel to reveal new insights into its physiology.

Na_V1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of Na_V1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.

Photoactivable toxins targeting ion channels have great potential to control cell activity. Here the authors report HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium channels; they validate this in cells, brain slices and in vivo on mice neuromuscular junctions.