NaV1.6 | sodium voltage-gated channel alpha subunit 8
Family:
Sodium channels
Subgroups:
NaV1.1-1.9
Topology:
Alpha subunits consist of four homologous domains (I-IV) with six transmembrane alpha helices (S1–S6) and a pore-forming loop. One a subunit may associate with 1 or 2 b subunits to make up the channel.
NaV1.6: Background Information
The NaV1.6 sodium channel is the most abundantly expressed isoform in the CNS during adulthood and is enriched at the axon initial segment and at the nodes of Ranvier. The channels are highly concentrated in sensory and motor axons in the peripheral nervous system. NaV1.6 facilitates action potential propagation when the membrane potential is depolarized by an influx of Na+ ions. However, NaV1.6 is able to sustain repetitive excitation and firing. The high frequency firing characteristic of NaV1.6 is caused by a persistent and resurgent sodium current. This characteristic is caused by slow activation of the sodium channel following repolarization, which allows a steady-state sodium current after the initial action potential propagation. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation. NaV1.6 is TTX-sensitive.
Gene:
SCN8A
Human Protein:
UniProt Q9UQD0
Tissue:
Brain central neurons, dorsal root ganglia, peripheral neurons, glia, Smooth muscle myocytes, corti organ, heart
Function/ Application:
Action potential initiation, propagation in excitable cells
Pathology:
Cognitive impairment with or without cerebellar ataxia (CIAT), epilepsy (EIEE13)
Interaction:
NEDD4, NEDD4L, β1, β2, β3, β4 subunit, calmodulin, FGF, MAPK14, ankyrin-G
Modulator:
Flecainide, ATX-II, Lidocaine
Assays:
Patch Clamp: whole cell, room temperature, State- and use-dependence
Particularities:
NaV channel analysis requires GigaOhm seals and a stable and low access resistance
Recommended Reviews:
International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol Rev 57: 397–409, Catterall, et al. 2005
Publications
2020 - Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Publication in Science Translational Medicine (2020)
Authors:
Heyne H.O., Baez-Nieto D., Iqbal S., Palmer D., Brunklaus A., Johannesen K.M., Lauxmann S., Lemke J.R., Møller R.S., Pérez-Palma E., Scholl U., Syrbe S., Lerche H., May P., Lal D., Campbell A.J., Pan J., Wang H.-R., Daly M.J.
2019 - Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) publication in Toxins (2019)
Authors:
Nicolas S., Zoukimian C., Bosmans F., Montnach J., Diochot S., Cuypers E., De Waard S., Béroud R., Mebs D., Craik D., Boturyn D., Lazdunski M., Tytgat J., De Waard M.
2017 - High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE
SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in PLoS One (2017)
Authors:
Li T, Lu G, Chiang E.Y., Chernov-Rogan T., Grogan J.L., Chen J.
2014 - Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy
Patchliner publication in Neurobiology of Disease (2014)
Authors:
Oliva M.K., McGarr T.C., Beyer B.J., Gazina E., Kaplan D.I., Cordeiro L., Thomas E., Dib-Hajj S.D., Waxman S.G., Frankel W.N., Petrou S.
2012 - Isolation, characterization and total regioselective synthesis of the novel μO-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels
Port-a-Patch publication in Biochemical Pharmacology (2012)
Authors:
Vetter I., Dekan Z., Knapp O., Adams D.J., Alewood P.F., Lewis R.J.