NaV1.2 | sodium voltage-gated channel alpha subunit 2
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.
NaV1.2: Background Information
NaV1.2 is primarily expressed in unmyelinated axons and dendrites. Besides other voltage gated sodium channels but predominately, NaV1.2 and NaV1.6 subunits are co-expressed within a single hair cell. NaV1.2 ion channels are regulated by neutrotransmitters that act through G-protein coupled receptors and activate protein kinase A such dopamine, acetylcholine and serotonin. NaV1.2 is sensitive to TTX.
Gene:
SCN2A
Human Protein:
UniProt Q99250
Tissue:
Brain (neurons, microglia), utricular hair cells, corti organ
Function/ Application:
Excitability of neurons, generation of action potentials
Pathology:
Autism, epilepsy (EIEE11, BFNIS), late ataxia, pain, myoclonus, multiple sclerosis, Seizures, benign familial infantile, 3, Ohtahara syndrome, Infantile Spasms
Interaction:
Ankyrin G, β1 subunit, β2 subunit, calmodulin, Nedd4-2
Modulator:
Tetrodotoxin, saxitoxin , β-scorpion toxin Css-IV, veratridine, α-scorpion toxin, ATX-II
Assays:
Patch Clamp: whole cell, room temperature, State- and use-dependence
Particularities:
Patch clamp: 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
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.
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.
2010 - Propranolol blocks cardiac and neuronal voltage-gated sodium channels
Patchliner publication in Frontiers in Pharmacology (2010)
Authors:
Wang D.W., Mistry A.M., Kahlig K.M., Kearney J.A, Xiang J., George Jr. A.L.