NaV1.1 | sodium voltage-gated channel alpha subunit 1
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.
NaV1.1: Background Information
NaV1.1 is a voltage-gated ion channel essential for the generation and propagation of action potentials, and is expressed in nerve, glial cells and muscle. In neurons NaV1.1 is presumably involved in propagating synaptic signals from dendrites to soma and in integration of electrical signals within the soma prior to the initiation of axonal action potentials. NaV1.1 is the primary voltage-gated Na+ channel in several clases of GABAergic interneurons, and its reduced activity leads to reduced excitability and decreased GABAergic tone. NaV1.1 is TTX-sensitive.
Gene:
SCN1A
Human Protein:
UniProt P35498
Tissue:
Brain (neurons, glia)
Function/ Application:
Excitability of neurons, generation of action potentials
Pathology:
Pain, epilepsy (SMEI, GEFS+), migraine (FHM3), Rasmussen's encephalitis, autism, Dravet syndrome, Lennox-Gastaut syndrome, Panayiotopoulos syndrome, Doose syndrome
Accessory subunits:
b1, b2, b3, b4
Interaction:
Alpha-1 syntrophin, β1 subunit, β2 subunit, calmodulin, Ca2+, FHF4
Modulator:
Tetrodotoxin, ATX-II, Bc-III, AFT-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
Webinars
08.05.2018 | Webinar: HTS Sodium Ion Channel Assays on the SyncroPatch 384PE
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i)
Learn about Sodium Ion Channel Assays on the SyncroPatch 384PE. Our speakers will present assays on NaV1.1, NaV1.7, NaV1.8 and NaV1.9:
- Biophysical and Pharmacological Characterization of Voltage-Gated Na Channels Involved in Pain Pathways.
- Identifying NaV1.1 Enhancers to Restore Inhibitory Interneuron Function in Dravet Syndrome and Alzheimer’s Disease.
03.11.2016 | External Webinar: Accelerating Ion Channel Characterization and New Drug Candidate Identification
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i)
This webinar will show high-throughput functional annotation of human ion channel variants associated with excitation disorders will be described along with use of the Syncropatch 384PE to measure subtype selective activation of KV7 potassium channels as well as inhibition of voltage gated sodium channels like NaV1.7, NaV1.1, and NaV1.5.
Organisation: Icagen Inc.
Publications
2020 - Fenamates Inhibit Human Sodium Channel Nav1.2 and Protect Glutamate-Induced Injury in SH-SY5Y Cells
Port-a-Patch publication in Cellular and Molecular Neurobiology (2020)
Authors:
Sun J.F., Zhao M.Y., Xu Y.J., Su Y., Kong X.H., Wang Z.Y.
2019 - 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.
2018 - Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death
Patchliner publication in PNAS (2018)
Authors:
Richards K.L., Milligan C.J., Richardson R.J., Jancovski N., Grunnet M., Jacobson L.H., Undheim E.A.B., Mobli M., Chow C.Y., Herzig V., Csoti A., Panyi G., Reid A.A., King G.F., Petrou S.
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.
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.
2010 - Multiplexed transposon-mediated stable gene transfer in human cells
Patchliner publication in Proc. Natl. Acad. Sci. USA. (2010)
Authors:
Kahlig K.M., Saridey S.K., Kaja A., Daniels M.A., George A.L. Jr., Wilson M.H.