SCN8A

(redirected from Nav1.6)

SCN8A

A gene on chromosome 12q13 that encodes an alpha subunit of the voltage-gated sodium channel, which mediates voltage-dependent sodium ion permeability of excitable membranes. The SCN8A protein product is required for rapid membrane depolarisation, resulting in action potentials in excitable neurones.

Molecular pathology
SCN8A mutations are associated with mental retardation, pancerebellar atrophy and ataxia.
References in periodicals archive ?
TALEN technology has been applied for modelling of epileptic encephalopathy in mice by introduction a missense mutation p.Asn1768Asp in Scn8a gene (sodium channel Nav1.6).
Xenon Pharmaceuticals provided clinical updates on XEN1101, a Kv7 potassium channel modulator being developed for the treatment of epilepsy and potentially other neurological disorders and XEN901, a potent, highly selective Nav1.6 sodium channel inhibitor being developed for the treatment of epilepsy.
Vijayalakshmi et al., "Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons," Brain Research, vol.
Zhang et al., "The up-regulation of voltage-gated sodium channel Nav1.6 expression following fluid percussion traumatic brain injury in rats," Neurosurgery, vol.
Waxman, "Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones," Journal of Physiology, vol.
The finding that a persistent current mediated by abnormally long regions of expression of Nav1.6 sodium channels triggers axonal degeneration in animal models of MS [4] has provided the basis for current clinical studies on sodium channel blockers as potential neuroprotective agents in MS [5].
For example, Nav1.6 is the variety present at the nodes of Ranvier, Nav1.5 is in the heart muscle, and others such as Navl.7, Nav1.8 and Nav1.9 are predominant in pain-sensing neurons.
XEN901 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed by Xenon for the treatment of epilepsy including treatment resistant adult and pediatric focal seizures, as well as rare, pediatric forms of epilepsy, such as EIEE13, an early infantile epileptic encephalopathy due to gain-of-function mutations in the SCN8A gene that encodes the Nav1.6 sodium channel.
A large variety of Nav subtypes from DRG cells, including tetrodotoxin- (TTX-) sensitive channels Nav1.1, Nav1.2, Nav1.6, and Nav1.7 and TTX-resistant channels Nav1.8 and Nav1.9, have been evaluated for involvement in epilepsy [35, 36].
"The Ataxia3 Mutation in the N-terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking." J.
Of the seven Nav isoforms expressed in nervous tissue [52], Nav1.6 is the predominant Nav at mature nodes of Ranvier in both the PNS and CNS [53-54], following a transition from Nav1.2, which is present along premyelinated axons and at immature nodes [53,55-57].
Using biomarkers to mark the damaged nerve fibers, they looked for molecular abnormalities within them and demonstrated a strong link between the presence of two molecules, Nav1.6 and NCX, and nerve damage.