Hormone-Induced Calcium Oscillations Depend on Cross-Coupling with Inositol 1,4,5-Trisphosphate Oscillations

• Main Authors: Lawrence D. Gaspers, Paula J. Bartlett, Antonio Politi, Paul Burnett, Walson Metzger, Jane Johnston, Suresh K. Joseph, Thomas Höfer, Andrew P. Thomas
• Format: Article
• Language: English
• Published: Elsevier 2014-11-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124714009024

Receptor-mediated oscillations in cytosolic Ca2+ concentration ([Ca2+]i) could originate either directly from an autonomous Ca2+ feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca2+ feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca2+ oscillations or could just be a secondary response to the [Ca2+]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 [Ca2+]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca2+]i rise and the speed of Ca2+ wave propagation and, at high levels, abolished [Ca2+]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca2+]i oscillations and waves.