Sodium Channel Protein Nav1.1 is encoded by the SCN1A gene on chromosome 2q24. It is a voltage-gated sodium channel (NaV1.1) primarily expressed in fast-spiking inhibitory interneurons. While classically associated with epilepsy and Dravet syndrome, Nav1.1 dysfunction is increasingly recognized in neurodegenerative conditions including Alzheimer's disease and ALS.
Structure
Protein Architecture
Length: 2008 amino acids
Molecular Weight: ~226 kDa
Domains:
Domain I (1-426): Voltage sensor and pore S1-S4
Domain II (427-853): Voltage sensor and pore S1-S4
Domain III (854-1245): Voltage sensor and pore S1-S4
Domain IV (1246-1622): Voltage sensor and pore S1-S4
C-terminal domain (1623-2008): Interaction domains and localization signals
Key Functional Regions
Normal Function
Action Potential Generation
Rapid Na+ influx during depolarization
Critical for action potential initiation in [neurons](/entities/neurons)
Essential for high-frequency firing in inhibitory interneurons
Controls neuronal excitability and network synchronization
Cellular Distribution
Predominantly expressed in GABAergic interneurons
Also present in pyramidal neurons (lower density)
Subcellular localization: axon initial segment, nodes of Ranvier
[@catterall2014]: [Pandey et al., Nav1.1 and neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/31141647/). Frontiers in Cellular Neuroscience. 2019;13:227.
[@yu2006]: [Verret et al., Interneuron dysfunction in AD](https://pubmed.ncbi.nlm.nih.gov/22832213/). Nature. 2012;486(7404):213-218.
[@wiser2000]: [Bender et al., Nav1.1 in ALS](https://pubmed.ncbi.nlm.nih.gov/23536069/). Brain. 2013;136(Pt 8):2432-2443.
[Catterall WA, Sodium channels, inherited epilepsy, and antiepileptic drugs (2014)](https://pubmed.ncbi.nlm.nih.gov/24717639/)
[Yu FH, et al, Sodium channel Nav1.1 is important for neuronal excitability in inhibitory neurons (2006)](https://pubmed.ncbi.nlm.nih.gov/17015841/)
[Wiser O, et al, Differential regulation of sodium channel expression by neuronal activity and seizures (2000)](https://pubmed.ncbi.nlm.nih.gov/10625705/)
[Meisler MH, et al, SCN1A mutations and epilepsy (2005)](https://pubmed.ncbi.nlm.nih.gov/15825079/)
[Escayg A, et al, Sodium channel SCN1A and Dravet syndrome (2011)](https://pubmed.ncbi.nlm.nih.gov/20809827/)
[Hedrich UB, et al, Impaired action potential firing in inhibitory neurons in a mouse model of Dravet syndrome (2014)](https://pubmed.ncbi.nlm.nih.gov/24849617/)
[Cheah CS, et al, Specific deletion of NaV1.1 in inhibitory neurons leads to seizures and sudden death (2012)](https://pubmed.ncbi.nlm.nih.gov/22683657/)
[Mistry AM, et al, Nav1.1 haploinsufficiency in inhibitory neurons enhances seizure susceptibility in a mouse model of Dravet syndrome (2014)](https://pubmed.ncbi.nlm.nih.gov/24966088/)
[Verret L, et al, Inhibitory interneuronon deficits contribute to a neuropsychiatric developmental disorder (2012)](https://pubmed.ncbi.nlm.nih.gov/22542153/)
[Palop JJ, et al, Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease (2007)](https://pubmed.ncbi.nlm.nih.gov/17668366/)