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

Lawrence D. Gaspers; Paula J. Bartlett; Antonio Politi; Paul Burnett; Walson Metzger; Jane Johnston; Suresh K. Joseph; Thomas Höfer; Andrew P. Thomas

doi:10.1016/j.celrep.2014.10.033

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

Lawrence D. Gaspers, Paula J. Bartlett, Antonio Politi, Paul Burnett, Walson Metzger, Jane Johnston, Suresh K. Joseph, Thomas Höfer, Andrew P. Thomas

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1209-1218
Number of pages	10
Journal	Cell Reports
Volume	9
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2014.10.033
State	Published - Nov 20 2014

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2014.10.033

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

abstract = "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.",

author = "Gaspers, {Lawrence D.} and Bartlett, {Paula J.} and Antonio Politi and Paul Burnett and Walson Metzger and Jane Johnston and Joseph, {Suresh K.} and Thomas H{\"o}fer and Thomas, {Andrew P.}",

note = "Funding Information: We acknowledge support from the NIH (DK082954 to A.P.T. and AA017752 to L.D.G.) and the Thomas P. Infusion Endowed Chair (to A.P.T.). IRIS-1 was generously provided by Dr. K. Mikoshiba. Publisher Copyright: {\textcopyright} 2014 The Authors.",

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AU - Gaspers, Lawrence D.

AU - Bartlett, Paula J.

AU - Politi, Antonio

AU - Burnett, Paul

AU - Metzger, Walson

AU - Johnston, Jane

AU - Joseph, Suresh K.

AU - Höfer, Thomas

AU - Thomas, Andrew P.

N1 - Funding Information: We acknowledge support from the NIH (DK082954 to A.P.T. and AA017752 to L.D.G.) and the Thomas P. Infusion Endowed Chair (to A.P.T.). IRIS-1 was generously provided by Dr. K. Mikoshiba. Publisher Copyright: © 2014 The Authors.

PY - 2014/11/20

Y1 - 2014/11/20

N2 - 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.

AB - 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.

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

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