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
2021 - The mechanism of non-blocking inhibition of sodium channelsrevealed by conformation-selective photolabeling
Port-a-Patch Publication in British Journal of Pharmacology (2021)
Authors:
Földi M.C., Pesti K., Zboray K., Toth A.V., Hegedűs T., Málnási‐Csizmadia A., Lukacs P., Mike A.
2020 - Mechanism of non-blocking inhibition of sodium channels revealed by conformation-selective photolabeling
Port-a-Patch pre-publication in BioRxiv (2020)
Authors:
Földi M.C., Pesti K., Zboray K., Hegedűs T., Málnási-Csizmadia A., Lukács P., Mike A.
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.
2018 - Non-blocking modulation contributes to sodium channel inhibition by a covalently attached photoreactive riluzole analog
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 - 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.
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
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
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
Port-a-Patch publication in Biochemical Pharmacology (2012)
Authors:
Vetter I., Dekan Z., Knapp O., Adams D.J., Alewood P.F., Lewis R.J.