| SCN4A (Nav1.4) | |
|---|---|
| Gene | SCN4A |
| UniProt | [Q9UI33](https://www.uniprot.org/uniprot/Q9UI33) |
| Protein Name | Sodium Voltage-Gated Channel Alpha Subunit 4 |
| PDB Structures | 6J8J, 7A5D |
| Molecular Weight | ~260 kDa |
| Subcellular Localization | Plasma Membrane (Skeletal Muscle) |
| Protein Family | Voltage-gated sodium channel (Nav), alpha subunit |
| Channel Type | Voltage-gated sodium channel |
| Ion Conducted | Na+ |
SCN4A Protein is a protein that in normal physiology, nav1.4 channels are responsible for the rapid depolarization of skeletal muscle fibers during action potential generation[1]. the channel undergoes conformational changes in response to membrane depolarization, leading to sodium ion influx and muscle contraction. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
The SCN4A protein encodes the alpha subunit of the voltage-gated sodium channel Nav1.4, which is primarily expressed in skeletal muscle[2]. The protein consists of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment serves as the voltage sensor, while the S5-S6 segments form the pore domain[3].
Key structural features include:
In normal physiology, Nav1.4 channels are responsible for the rapid depolarization of skeletal muscle fibers during action potential generation[1:1]. The channel undergoes conformational changes in response to membrane depolarization, leading to sodium ion influx and muscle contraction.
Key functions include:
While SCN4A is primarily a skeletal muscle channel, it has several connections to neurodegenerative processes:
The SCN4A channel is targeted by several drug classes:
| Drug Class | Examples | Mechanism | Neurodegeneration Relevance |
|---|---|---|---|
| Class I Antiarrhythmics | Mexiletine, Flecainide | Use-dependent block | Myotonia treatment, potential neuroprotection |
| Local Anesthetics | Lidocaine, Carbamazepine | Pore block | Pain management in neuropathy |
| Natural Toxins | Tetrodotoxin, Saxitoxin | High-affinity pore block | Research tools |
| Experimental | Ranolaridine | State-dependent block | Investigational |
SCN4A Protein (Nav1.4) is Sodium channel, voltage-gated, type IV. It plays roles in neuronal function and has been implicated in various neurological conditions.
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