The Journal of Membrane Biology

, Volume 245, Issue 2, pp 117–123

Ancient Origin of Four-Domain Voltage-gated Na+ Channels Predates the Divergence of Animals and Fungi



The four-domain voltage-gated Na+ channels are believed to have arisen in multicellular animals, possibly during the evolution of the nervous system. Recent genomic studies reveal that many ion channels, including Na+ channels and Ca2+ channels previously thought to be restricted to animals, can be traced back to one of the unicellular ancestors of animals, Monosiga brevicollis. The eukaryotic supergroup Opisthokonta contains animals, fungi, and a diverse group of their unicellular relatives including M. brevicollis. Here, we demonstrate the presence of a putative voltage-gated Na+ channel homolog (TtrNaV) in the apusozoan protist Thecamonas trahens, which belongs to the unicellular sister group to Opisthokonta. TtrNaV displays a unique selectivity motif distinct from most animal voltage-gated Na+ channels. The identification of TtrNaV suggests that voltage-gated Na+ channels might have evolved before the divergence of animals and fungi. Furthermore, our analyses reveal that NaV channels have been lost independently in the amoeboid holozoan Capsasporaowczarzaki of the animal lineage and in several basal fungi. These findings provide novel insights into the evolution of four-domain voltage-gated ion channels, ion selectivity, and membrane excitability in the Opisthokonta lineage.


Channel evolution Channel pore Genomics Na+ channel Protists Selectivity motif 

Supplementary material

232_2012_9415_MOESM1_ESM.tif (6.6 mb)
Fig. S1. Phylogenetic analysis of NaV and CaV channel homologs by using the four-domain human NALCN channel as the outgroup. Phylogenetic analysis was performed as shown in Fig. 2 legend. Bootstrap values greater than 60 are shown at the nodes. For species abbreviations, see Fig. 2 legend (TIFF 6759 kb)
232_2012_9415_MOESM2_ESM.tif (6.8 mb)
Fig. S2. Phylogenetic analysis of NaV and CaV channel homologs by using two prokaryotic single domain voltage-dependent NaV channels as the outgroup. The phylogenetic three was constructed as shown in Fig. 2 legend. Bootstrap values greater than 60 are shown at the nodes. For species abbreviations, see Fig. 2 legend (TIFF 7012 kb)


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Molecular PathogenesisNew York University Langone Medical CenterNew YorkUSA

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