The evolution of pentameric ligand-gated ion channels

Fast, ionotropic neurotransmission mediated by ligand-gated ion channels is essential for timely behavioral responses in multicellular organisms. Metazoa employ more ionotropic neurotransmitters in more types of synapses, inhibitory or excitatory, than is generally appreciated. It is becoming increasingly clear that the adaptability of a single neurotransmitter receptor superfamily, the pentameric ligand-gated ion channels (pLGICs), makes the diversity in ionotropic neurotransmission possible. Modification ofa common pLGIC structure generates channels that are gated by ligands as different as protons, histamine or zinc and that pair common neurotransmitters with both cation and anion permeability. A phylogeny of the pLGIC gene family from representative metazoa suggests that pLGIC diversity is ancient and evolution of contemporary phyla was characterized by a surprising loss of pLGIC diversity. The pLGIC superfamily reveals aspects of early metazoan evolution, may help us identify novel neurotransmitters and can inform our exploration of structure/function relationships.