NaV1.4 | sodium voltage-gated channel alpha subunit 4

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.

 

NaV1.4: Background Information

NaV1.4 is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. One of the changes that helps trigger muscle contractions is the flow of positively charged ions, including sodium, into muscle cells. NaV1.4 ion channel controls the flow of sodium ions into these cells. NaV1.4 is TTX-sensitive.

Gene:
SCN4A

Human Protein:
UniProt P35499

Tissue:
Skeletal muslce

Function/ Application:
Generation and propagation of action potentials in muscle

Pathology:
Myotonia (PMC, PAM), periodic paralysis (HyperPP, HypoPP), congenital myasthenic syndrome

Interaction:
β1 subunit, syntrophin, calmodulin, DISC

Modulator:
Tetrodotoxin, saxitoxin, veratridine, grayanotoxin, 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 

Publications

2018 - Non-blocking modulation contributes to sodium channel inhibition by a covalently attached photoreactive riluzole analog

icon pap   Port-a-Patch publication in Nature Scientific Reports (2018)

Authors:
Lukacs P., Mátyás F.C., Valánszki L., Casanova E., Biri-Kovács B., Nyitray L., Málnási-Csizmadia A., Mike A.

2017 - A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity

icon pap   Port-a-Patch publication in Journal of Biological Chemistry (2017)

Authors:
Xu Y., Meng X., Hou X., Sun J., Kong X., Sun Y., Liu Z., Ma Y., Niu Y., Song Y., Cui Y., Zhao M., Zhang J.

2015 - The Functional Property Changes of Muscular Nav1.4 and Cardiac Nav1.5 Induced by Scorpion Toxin BmK AGP-SYPU1 Mutants Y42F and Y5F

icon pap  Port-a-Patch publication in Biochemistry (2015)

Authors: 
Meng x., Xu Y., Zhao M., Wang F., Ma Y., Jin Y., Liu Y., Song Y., Zhang J.

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.

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