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

icon sp96   SyncroPatch 384PE

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

icon sp96   SyncroPatch 384PE

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

2018 - Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death

icon pl   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.

2012 - Isolation, characterization and total regioselective synthesis of the novel μO-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels

icon pap   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

icon pl  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

icon pl  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.

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