1. Cell Biology
  2. Structural Biology and Molecular Biophysics
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IP3 mediated global Ca2+ signals arise through two temporally and spatially distinct modes of Ca2+ release

  1. Jeffrey T Lock  Is a corresponding author
  2. Ian Parker
  1. University of California, Irvine, United States
Research Article
  • Cited 6
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Cite this article as: eLife 2020;9:e55008 doi: 10.7554/eLife.55008


The 'building-block' model of inositol trisphosphate (IP3)-mediated Ca2+ liberation posits that cell-wide cytosolic Ca2+ signals arise through coordinated activation of localized Ca2+ puffs generated by stationary clusters of IP3 receptors (IP3Rs). Here, we revise this hypothesis, applying fluctuation analysis to resolve Ca2+ signals otherwise obscured during large Ca2+ elevations. We find the rising phase of global Ca2+ signals is punctuated by a flurry of puffs, which terminate before the peak by a mechanism involving partial ER Ca2+ depletion. The continuing rise in Ca2+, and persistence of global signals even when puffs are absent, reveal a second mode of spatiotemporally diffuse Ca2+ signaling. Puffs make only small, transient contributions to global Ca2+ signals, which are sustained by diffuse release of Ca2+ through a functionally distinct process. These two modes of IP3-mediated Ca2+ liberation have important implications for downstream signaling, imparting spatial and kinetic specificity to Ca2+-dependent effector functions and Ca2+ transport.

Data availability

Algorithms used to generate SD fluctuation images from Ca2+ image recordings are provided in the Supplementary file 1.

Article and author information

Author details

  1. Jeffrey T Lock

    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1522-3189
  2. Ian Parker

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.


National Institute of General Medical Sciences (R37 GM048071)

  • Ian Parker

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton J Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: January 9, 2020
  2. Accepted: May 12, 2020
  3. Accepted Manuscript published: May 12, 2020 (version 1)
  4. Version of Record published: May 27, 2020 (version 2)


© 2020, Lock & Parker

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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