Convergent Evolution of Sodium Ion Selectivity in Metazoan Neuronal Signaling

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. [Display omitted] ► Na+ channel homologs that conduct Ca2+ appeared more than a billion years ago ► Na+ selectivity evolved separately in Cnidaria and Bilateria ► Na+ selectivity is conferred by structural differences at the channel pore Moran and colleagues have now characterized sodium channel homologs from a sea anemone, revealing four members with a preference for calcium ion conductance, as well as a sodium-selective channel. Sodium selectivity in this channel is conferred by a selectivity filter and pore structure that differ from those of higher animals (Bilateria). A phylogenetic analysis indicates that sodium selectivity in Cnidaria (sea anemones, corals, and jellyfish) evolved independently from that in Bilateria >540 million years ago, reflecting requirements for improved neuronal signaling in a changing environment.