NaV1.6 | sodium voltage-gated channel alpha subunit 8

Family:
Sodium channels

Subgroups:
Na_V1.1-1.9

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 Na_V1.6 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. Na_V1.6 facilitates action potential propagation when the membrane potential is depolarized by an influx of Na+ ions. However, Na_V1.6 is able to sustain repetitive excitation and firing. The high frequency firing characteristic of Na_V1.6 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. Na_V1.6 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:
Na_V 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

2019 - Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium

SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Pre-publication in bioRxiv Biology (2019)

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.

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.