title: Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.
abstract: HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa) to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps.
authors.affiliation: Department of Biology, Penn State University, University Park, Pennsylvania, United States of America.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Baker
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Layden
authors.affiliation: Department of Biology, Penn State University, University Park, Pennsylvania, United States of America.|Huck Institutes of the Life Sciences, University Park, Pennsylvania, United States of America.
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.affiliation: Department of Biology, Penn State University, University Park, Pennsylvania, United States of America.
authors.forename: Bishoy
authors.initials: B
authors.lastname: Kamel
authors.affiliation: Department of Biology, Penn State University, University Park, Pennsylvania, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Medina
authors.affiliation: Penn State University Graduate School, Summer Research Opportunities Program (SROP), University Park, Pennsylvania, United States of America.
authors.forename: Eboni
authors.initials: E
authors.lastname: Simpson
authors.affiliation: Department of Biology, Penn State University, University Park, Pennsylvania, United States of America.|Huck Institutes of the Life Sciences, University Park, Pennsylvania, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Jegla
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003063:Cnidaria / Q000378:metabolism*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D007473:Ion Channels