TY - JOUR T1 - Ion Channel Clustering at the Axon Initial Segment and Node of Ranvier Evolved Sequentially in Early Chordates A1 - Hill, Alexis S. A1 - Nishino, Atsuo A1 - Nakajo, Koichi A1 - Zhang, Giuxin A1 - Fineman, Jaime R. A1 - Selzer, Michael E. A1 - Okamura, Yasushi A1 - Cooper, Edward C. Y1 - 2008/12/26 N2 - Author Summary Because nervous systems generate behavior, innovations that confer new neuronal signaling functions are important potential factors in evolution. In mammals, clustering of ion channels on nerves is essential for electrical impulses used in rapid signaling. This channel clustering is generally absent in insects, worms, and other non-chordates. We traced the evolutionary emergence of mechanisms underlying channel clustering on nerves by analyzing the genomes of primitive chordates and studying the cellular distribution and functional properties of their channels. We found that sodium channel clustering evolved early in the chordate lineage, before the divergence of the earliest wormlike and planktonic groups (lancelets and sea squirts). Nerve fibers of the lamprey, a primitive fish, retained some invertebrate features but possessed dense sodium channel clusters like in more recently evolved vertebrates. A potassium channel clustering system evolved, after the divergence of lampreys, in a common ancestor of shark and humans. We conclude that the clustering of sodium channels on axons was the initial pivotal step in a chordate-specific series of evolutionary innovations, making nerve impulses more rapid and robust. The refinements in action potentials we have elucidated appear essential for the complex neural signaling and active behavior of vertebrates. JF - PLOS Genetics JA - PLOS Genetics VL - 4 IS - 12 UR - https://doi.org/10.1371/journal.pgen.1000317 SP - e1000317 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1000317 ER -