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Last update 23 Jan 2025

SCN4A

Last update 23 Jan 2025

Basic Info

Synonyms

HYKPP, HYPP, Nav1.4

+ [10]

Introduction

Pore-forming subunit of a voltage-gated sodium channel complex through which Na(+) ions pass in accordance with their electrochemical gradient. Alternates between resting, activated and inactivated states (PubMed:12766226, PubMed:29992740, PubMed:30190309, PubMed:15318338, PubMed:16890191, PubMed:18690054, PubMed:17898326, PubMed:19347921, PubMed:25707578, PubMed:26700687). Required for normal muscle fiber excitability, normal muscle contraction and relaxation cycles, and constant muscle strength in the presence of fluctuating K(+) levels (PubMed:12766226, PubMed:15318338, PubMed:16890191, PubMed:19347921, PubMed:25707578, PubMed:26700687, PubMed:26659129).

Drugs associated with SCN4A

Neosaxitoxin

Target

SCN4A

Mechanism

SCN4A blockers

Active Org.-

Originator Org.

Grunenthal SA

Active Indication-

Inactive Indication

Anesthesia

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ST-410

Target

SCN4A

Mechanism

SCN4A blockers

Active Org.-

Originator Org.

SiteOne Therapeutics, Inc.

Active Indication-

Inactive Indication

Pain

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SCN4A

NCT03399435

/ TerminatedPhase 1

An Exploratory Phase I Randomized, Single-site, Double-blind, Active-controlled, Parallel-group, Single-administration, Dose-escalation Trial to Investigate the Safety and Tolerability of Neosaxitoxin Alone and in Combination With Bupivacaine (With and Without Epinephrine), in Perineural Administrations for Brachial Plexus Blockade in Healthy Subjects

Neosaxitoxin is a new compound that is in clinical development as local anesthetic for surgical anesthesia and postoperative analgesia.
The primary objective of this study is to evaluate the systemic and local safety and tolerability of ascending doses of neosaxitoxin alone and in combination with fixed doses of bupivacaine (with and without epinephrine), following brachial plexus blockade in healthy male subjects.
Secondary objectives:
Evaluate the pharmacodynamics (PD) of ascending doses of neosaxitoxin, alone and in combination with fixed doses of bupivacaine (with and without epinephrine), following brachial plexus blockade.
Characterize the pharmacokinetics (PK) of neosaxitoxin and bupivacaine after brachial plexus blockade with neosaxitoxin alone or different drug combinations: neosaxitoxin and epinephrine, neosaxitoxin and bupivacaine, or neosaxitoxin and bupivacaine and epinephrine.

Start Date30 Jan 2018

Sponsor / Collaborator

Grünenthal GmbH

NCT01786655

/ CompletedPhase 1IIT

Neosaxitoxin (NeoSTX) Alone and in Combination With Bupivacaine as Prolonged Duration Local Anesthetics: A Phase I Investigator-initiated Dose Escalation Study

The primary aim of this Phase 1 study is to evaluate the systemic safety of a novel prolonged-duration local anesthetic, Neosaxitoxin (NeoSTX), given by subcutaneous injection in combination with the commonly used local anesthetic, bupivacaine, and epinephrine.
The investigators hypothesize that a "minimal adverse effect threshold" NeoSTX dose for subcutaneous administration in combination with bupivacaine 0.2% and epinephrine 5mcg/ml respectively, can be defined for awake, young adult healthy volunteer subjects. At the same time, the pharmacokinetics of NeoSTX when delivered subcutaneously will be determined.

Start Date01 May 2013

Sponsor / Collaborator

The Children's Hospital Corp.

NCT00273065

/ CompletedPhase 1

Phase 1 Study of Local Infiltration of Neosaxitoxin as a Local Anesthetic

The purpose of this study is to evaluate the local anesthetic properties of neosaxitoxin in humans

Start Date01 May 2005

Sponsor / Collaborator

University of Chile

100 Clinical Results associated with SCN4A

100 Translational Medicine associated with SCN4A

0 Patents (Medical) associated with SCN4A

738

Literatures (Medical) associated with SCN4A

01 Feb 2025·Poultry Science

Exploring variances in meat quality between Qingyuan partridge chicken and Cobb broiler: Insights from combined multi-omics analysis

Article

Author: Li, Zhenhui ; Cai, Bolin ; Wu, Ruiquan ; Zhang, Zhaofeng ; Cai, Danfeng ; Kong, Shaofen ; Mo, Yu ; Yang, Xin ; Zhou, Zhen ; Nie, Qinghua ; Zhang, Ruitong

Previously, animal breeding prioritized enhancing key economic traits to improve production efficiency, leading to a gradual difference in meat quality. However, the genetic factors influencing meat quality remain unclear. To identify key genetic pathways contributing to meat quality, native Chinese yellow-feathered chicken (Qingyuan Partridge Chicken, QPC; female, n=10), and commercial chicken broiler (Cobb broiler, CB; female, n=10) were used for meat quality assessment through metabolomics, proteomics, and phosphoproteomics sequencing. The results show that QPC had lower pH (93.12%), shear force (81.46%), cooking loss (69.29%), moisture content (93.24%) and muscle fiber area (46.04%), but higher meat color values (a*(163.65%) and b*(250.27%)), drip loss (146.32%), and intramuscular fat content (382.01%) than CB (p < 0.05). Metabolomic, proteomic, and phosphoproteomic analyses were jointly conducted, revealing significant differences in energy metabolism strategies. Higher glycolytic enzyme activity was observed in QPC (ENO1, GAPDH, GPI, PFKM, PKM, and TPI1, p < 0.05), while more energetic phosphate compounds were stored in CB. CB had higher Na⁺/K⁺ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca²⁺ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC. In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca²⁺. These results suggest CB is more contractile than QPC, contributing to meat quality between CB and QPC.

01 Feb 2025·Neurology Genetics

A Case Report

Article

Author: Ralph, Jeffrey W. ; Rosow, Laura ; Margeta, Marta ; Tugizova, Madina ; Terrelonge, Mark ; Richie, Megan ; Pet, Douglas

ObjectivesTo report a case of adult-onset non-dystrophic myotonia complicated by recurrent episodes of laryngospasm.MethodsThe patient is a 35-year-old man who was admitted to our hospital for recurrent episodes of apnea requiring endotracheal intubation with mechanical ventilation. He underwent extensive evaluation, including EMG, laryngoscopy, muscle biopsy, and genetic testing, which revealed a diagnosis of non-dystrophic myotonia.ResultsHis myotonic disorder was due to the synergistic effects of a pathogenic CLCN1 variant and a newly reported SCN4A variant. His muscle biopsy demonstrated myofibrillar disorganization with Z-band streaming, which may reflect the severity of his clinical and electrographic myotonia. Treatment with mexiletine resulted in resolution of his episodes of laryngospasm and symptoms of myotonia in the extremities.DiscussionOur case adds to the literature on the potentiating effects of chloride channelopathies on sodium channel myotonia. This is the first reported case of an adult-onset sodium channelopathy manifesting with respiratory failure due to laryngospasm. In addition, we present muscle biopsy findings that have not been described in the recent literature. This case also highlights that a myotonic disorder should be considered in the differential diagnosis for recurrent episodes of mixed hypoxic and hypercarbic respiratory failure.

01 Jan 2025·Journal of Biological Chemistry

Multiple gating processes associated with the distal end of the S6 segment of domain II in the Nav channels

Article

Author: Chen, Minzhi ; Xiao, Zhen ; Peng, Shuijiao ; Liu, Zhonghua ; Zhou, Xi

Voltage-gated sodium (Nav) channels are transmembrane proteins that play crucial roles in the initiation and propagation of action potentials (APs) in excitable tissues such as the heart, muscles, and nerves. The distal ends of the four domain S6 segments of Nav channels contain hydrophobic residues, which form an intracellular gate. This gate allows Nav channels to control ion flux in excitable cells by opening and closing. However, the mechanism of the distal end of Domain II (DII) S6 segment in channel gating remains unclear. In this study, using whole-cell patch clamp recording, we systematically investigated the biophysical characteristics of various mutants L811 site (located at the distal end of the DII S6 segment) of Nav1.9 and the corresponding L796P mutant of Nav1.4. We found that the mutations significantly shifted the activation and inactivation curves, slowed the fast inactivation, accelerated the slow inactivation and use-dependent slow inactivation, and L811P altered the ion selectivity of the channel. Therefore, our findings suggest that the distal end of the DII S6 segment in Nav channels plays a pivotal role in regulating multiple gating processes.

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SCN4A

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