Overview of the voltage-gated sodium channel family
Open accessAbstract
Selective permeation of sodium ions through voltage-dependent sodium channels is fundamental to the generation of action potentials in excitable cells such as neurons. These channels are large integral membrane proteins and are encoded by at least ten genes in mammals. The different sodium channels have remarkably similar functional properties, but small changes in sodium-channel function are biologically relevant, as underscored by mutations that cause several human diseases of hyperexcitability.
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Voltage-gated sodium channels evolved from a calcium channel early in animal evolution, and the DEKA ion selectivity filter in NaV1 derives from the ancestral DEEA filter.
“Voltage-gated sodium channels (NaV) are derived from a calcium channel (CaV3) early in the evolution of animals [42–44] with the DEKA ion selectivity filter in NaV1 being derived from the ancestral DEEA filter (Figure 3, Table 3).”
From Progress in Understanding and Treating SCN2A-Mediated Disorders (2018) · cites this paper as [43]
The “Evolutionary history and sodium channel genes” section says four-domain sodium channels evolved from calcium channels and appeared around the evolution of metazoans. It does not identify CaV3 as the ancestor. “Molecular basis of function” identifies DEKA as the sodium-channel selectivity-filter residues and compares them with EEEE in calcium channels, but does not say that DEKA derives from an ancestral DEEA filter. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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“(A) Voltagegated sodium channels (NaV) are derived from T-type voltage-gated calcium channels (CaV3) [42,43].”
BackgroundSelf-citationDifferential evolution of voltage-gated sodium channels in tetrapods and teleost fishes
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Letter to the editor: confirming neonatal seizure and late onset ataxia in SCN2A Ala263Val
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- Authors
- Yu
- Venue
- Genome biology
- Published
- 2003
- Volume
- 4
- Issue
- 3
- Pages
- 207
- ISSN
- 1465-6906 (ISSN-L)
- PMC
- PMC153452
- OpenAlex
- W2152845515
- Cited by
- 694
- References
- 56
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 28 · 2023: 32 · 2022: 34 · 2021: 36 · 2020: 26 · 2019: 31 · 2018: 37 · 2017: 32 · 2016: 29 · 2015: 37 · 2014: 34 · 2013: 37 · 2012: 44
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- voltage-gated sodium channels, sodium channel gene, sodium ion permeation, action potential, excitable cells, sodium channel mutations, integral membrane proteins
- MeSH terms
- Action Potentials, Animals, Multigene Family, Humans, Synaptic Transmission, Sodium Channels, Ion Channel Gating, Evolution, Molecular
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