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 Ca(2+) 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 (TtrNa(V)) in the apusozoan protist Thecamonas trahens, which belongs to the unicellular sister group to Opisthokonta. TtrNa(V) displays a unique selectivity motif distinct from most animal voltage-gated Na(+) channels. The identification of TtrNa(V) suggests that voltage-gated Na(+) channels might have evolved before the divergence of animals and fungi. Furthermore, our analyses reveal that Na(V) channels have been lost independently in the amoeboid holozoan Capsaspora owczarzaki 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. © Springer Science+Business Media, LLC 2012