A-type fibroblast growth factor homologous factors generate resurgent currents in tetrodotoxin-resistant voltage-gated sodium channels, increase repetitive firing of sensory neurons, and provide a potentially important target for pain treatment strategies.

NBI-921352 (formerly XEN901) is a precision medicine in development for individuals with SCN8A gain-of-function mutations causing SCN8A related epilepsy syndrome (SCN8A-RES), as well as other epilepsy indications, include adult focal onset seizures (FOS).

The voltage-gated sodium channel Na_v1.1 is identified as an essential component of the proprioceptive transmission machinery that is required in vivo for normal motor behavior.

In neocortex, Nav1.1 is expressed in neocortical pyramidal tract projection neurons and a minor subpopulation of cortico-cortical projection neurons in addition to its predominant expression in inhibitory neurons, while the majority of cortico-thalamic, cortico-striatal, and cortico-cortical neurons express Nav1.2.

Human sensory neurons may not only bridge a critical gap between drug discovery and clinical trials, but force a re-evaluation of basic assumptions about the mechanisms controlling primary afferent excitability.

Vasoactive intestinal peptide-expressing GABAergic interneurons in cerebral cortex express the sodium channel subunit Nav1.1, and a defined subset of VIP interneurons are dysfunctional in a mouse model of Dravet syndrome.

Because nociceptors can achieve similar excitability using different sodium channel subtypes, it is difficult to know which channels are being used yet this information is critical for predicting if subtype-selective drugs will reduce pain.

Experimental and modeling results reveal that the activation of resurgent sodium currents relies on the recovery of inactivated channels into a conducting state, and that the decay of resurgent currents reflects the accumulation of these channels into a slow-inactivated state.

Simulations reveal where phosphoinositide lipids bind to voltage-gated sodium channels and how they reduce channel activity.

The high resolution crystal structure and electrophysiology of a sodium channel complex with cannabidiol, a drug approved for treatment of severe epilepsies, demonstrate the basis for its structural- functional effects.