Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.

Authors

Lawrence D Gaspers, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey
Paula J Bartlett, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey
Antonio Politi, German Cancer Research Center, Division of Theoretical Systems Biology
Paul Burnett, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey
Walson Metzger, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey
Jane Johnston, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey
Suresh K Joseph, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson UniversityFollow
Thomas Höfer, German Cancer Research Center, Division of Theoretical Systems Biology
Andrew P Thomas, Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, The State University of New Jersey

Document Type

Article

Publication Date

11-20-2014

Comments

This article has been peer reviewed. It was published in: Cell Reports.

Volume 9, Issue 4, 20 November 2014, Pages 1209-1218.

The published version is available at DOI: 10.1016/j.celrep.2014.10.033

Copyright © 2014 The Authors.

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.

Recommended Citation

Gaspers, Lawrence D; Bartlett, Paula J; Politi, Antonio; Burnett, Paul; Metzger, Walson; Johnston, Jane; Joseph, Suresh K; Höfer, Thomas; and Thomas, Andrew P, "Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations." (2014). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 155.
https://jdc.jefferson.edu/pacbfp/155

PubMed ID

25456123