Ion selectivity of metazoan voltage-gated Na+ channels is critical for neuronal signaling and has long been attributed to a ring of four conserved amino acids that constitute the ion selectivity filter (SF) at the channel pore. Yet, in addition to channels with a preference for Ca2+ ions, the expression and characterization of Na+ channel homologs from the sea anemone Nematostella vectensis, a member of the early-branching metazoan phylum Cnidaria, revealed a sodium-selective channel bearing a noncanonical SF. Mutagenesis and physiological assays suggest that pore elements additional to the SF determine the preference for Na+ in this channel. Phylogenetic analysis assigns the Nematostella Na+-selective channel to a channel group unique to Cnidaria, which diverged >540 million years ago from Ca2+-conducting Na+ channel homologs. The identification of Cnidarian Na+-selective ion channels distinct from the channels of bilaterian animals indicates that selectivity for Na+ in neuronal signaling emerged independently in these two animal lineages.
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Jensen, L. D., Cao, Z., Nakamura, M., Yang, Y., Bräutigam, L., Andersson, P., … Cao, Y. (2012). Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish. Cell Reports, 2(2), 231–241. https://doi.org/10.1016/j.celrep.2012.07.005
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