title: Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA.
abstract: Atlantic killifish (Fundulus heteroclitus) thrive in New Bedford Harbor (NBH), MA, highly contaminated with polychlorinated biphenyls (PCBs). Resident killifish have evolved tolerance to dioxin-like (DL) PCBs, whose toxic effects through the aryl hydrocarbon receptor (AhR) are well studied. In NBH, non-dioxin like PCBs (NDL PCBs), which lack activity toward the AhR, vastly exceed levels of DL congeners yet how killifish counter NDL toxic effects has not been explored. In mammals and fish, NDL PCBs are potent activators of ryanodine receptors (RyR), Ca(2+) release channels necessary for a vast array of physiological processes. In the current study we compared the expression and function of RyR related pathways in NBH killifish with killifish from the reference site at Scorton Creek (SC, MA). Relative to the SC fish, adults from NBH displayed increased levels of skeletal muscle RyR1 protein, and increased levels of FK506-binding protein 12 kDa (FKBP12) an accessory protein essential for NDL PCB-triggered changes in RyR channel function. In accordance with increased RyR1 levels, NBH killifish displayed increased maximal ligand binding, increased maximal response to Ca(2+) activation and increased maximal response to activation by the NDL PCB congener PCB 95. Compared to SC, NBH embryos and larvae had increased levels of mtor and ryr2 transcripts at multiple stages of development, and generations, while levels of serca2 were decreased at 9 days post-fertilization in the F1 and F2 generations. These findings suggest that there are compensatory and heritable changes in RyR mediated Ca(2+) signaling proteins or potential signaling partners in NBH killifish.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. Electronic address: ebholland@ucdavis.edu.
authors.forename: Erika B
authors.initials: EB
authors.lastname: Fritsch
authors.affiliation: Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Stegeman
authors.affiliation: Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.
authors.forename: Jared V
authors.initials: JV
authors.lastname: Goldstone
authors.affiliation: Atlantic Ecology Division, Office of Research and Development, US Environmental Protection Agency, Narragansett, RI, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Nacci
authors.affiliation: Atlantic Ecology Division, Office of Research and Development, US Environmental Protection Agency, Narragansett, RI, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Champlin
authors.affiliation: Atlantic Ecology Division, Office of Research and Development, US Environmental Protection Agency, Narragansett, RI, USA.
authors.forename: Saro
authors.initials: S
authors.lastname: Jayaraman
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Connon
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA; The Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Medical Center, Sacramento, USA.
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
mesh_terms: D000818:Animals; D004361:Drug Tolerance / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D023781:Fundulidae / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008404:Massachusetts; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls
keywords: Fundulus heteroclitus; Non-dioxin like PCBs; PCB tolerance; Ryanodine receptor