Adaptive evolution of voltage-gated sodium channels : the first 800 million years

Thumbnail Image
Zakon, Harold H.
Linked Authors
Date Created
Replaced By
Voltage-gated Na+-permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca2+ channels and were present in the common ancestor of choanoflagellates and animals although this channel was likely permeable to both Na+ and Ca2+. Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1, 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, 50MY 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 (~9-10 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).
Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 109 (2012): 10619-10625, doi:10.1073/pnas.1201884109.
Embargo Date
Cruise ID
Cruise DOI
Vessel Name