Adaptive evolution of voltage-gated sodium channels: The first 800 million years
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Voltage-gated Na + -permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca 2+ channels and were present in the common ancestor of choanoflagellates and animals, although this channel was likely permeable to both Na + and Ca 2+ . Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Approximately 500 Mya in early chordates Nav channels evolved a motif that allowed them to cluster at axon initial segments, 50 million years later with the evolution of myelin, Nav channels “capitalized” on this property and clustered at nodes of Ranvier. The enhancement of conduction velocity along with the evolution of jaws likely made early gnathostomes fierce predators and the dominant vertebrates in the ocean. Later in vertebrate evolution, the Nav channel gene family expanded in parallel in tetrapods and teleosts (∼9 to 10 genes in amniotes, 8 in teleosts). This expansion occurred during or after the late Devonian extinction, when teleosts and tetrapods each diversified in their respective habitats, and coincided with an increase in the number of telencephalic nuclei in both groups. The expansion of Nav channels may have allowed for more sophisticated neural computation and tailoring of Nav channel kinetics with potassium channel kinetics to enhance energy savings. Nav channels show adaptive sequence evolution for increasing diversity in communication signals (electric fish), in protection against lethal Nav channel toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats).
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Proteins required for action potential generation and propagation were present in early metazoans, such as voltage-gated sodium, potassium and calcium channels.
“Proteins required for action potential generation and propagation were likewise present in early metazoans, such as voltage-gated sodium [28,29], potassium and calcium channels [30].”
From Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution (2015) · cites this paper as [29]
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Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution
Arendt, D., Benito-Gutierrez, E., Brunet, T., & Marlow, H. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0286 · Cited by 112 · see citing works
- Authors
- Zakon, H. H.
- Affiliations
- Marine Biological Laboratory (US)
- Corresponding author
- Zakon, Harold H.
- ORCID
- Zakon, Harold H.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-06-22
- Volume
- 109
- Issue
- supplement_1
- Pages
- 10619-10625
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3386883
- OpenAlex
- W2070893625
- Cited by
- 156
- References
- 69
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 16 · 2020: 9 · 2019: 14 · 2018: 9 · 2017: 13 · 2016: 15 · 2015: 15 · 2014: 9 · 2013: 11 · 2012: 4
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS025513)
- 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, electrical excitability, axon initial segment, nodes of Ranvier, myelination, conduction velocity, teleosts, tetrapods, Devonian extinction, electric fish, naked mole-rat, choanoflagellates, vertebrate evolution
- MeSH terms
- Adaptation, Physiological, Amino Acid Sequence, Animals, Axons, Biological Evolution, Humans, Molecular Sequence Data, Vertebrates, Sodium Channels, Gene Duplication, History, Ancient
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