title: Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.
abstract: Receptor-mediated oscillations in cytosolic Ca(2+) concentration ([Ca(2+)]i) could originate either directly from an autonomous Ca(2+) feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca(2+) feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca(2+) oscillations or could just be a secondary response to the [Ca(2+)]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state [IP3]. GFP-LBD perturbed [Ca(2+)]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca(2+)]i rise and the speed of Ca(2+) wave propagation and, at high levels, abolished [Ca(2+)]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca(2+)]i oscillations and waves.
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Gaspers
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Bartlett
authors.affiliation: German Cancer Research Center, Division of Theoretical Systems Biology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Politi
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Burnett
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Walson
authors.initials: W
authors.lastname: Metzger
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Johnston
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Joseph
authors.affiliation: German Cancer Research Center, Division of Theoretical Systems Biology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA. Electronic address: andrew.thomas@rutgers.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Thomas
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D014667:Vasopressins; D049452:Green Fluorescent Proteins; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium