Inositol (1,4,5)-trisphosphate receptor microarchitecture shapes Ca 2+ puff kinetics

Luis Diambra, Jonathan S. Marchant

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Inositol (1,4,5)-trisphosphate receptors (IP3Rs) release intracellular Ca2+ as localized Ca2+ signals (Ca 2+ puffs) that represent the activity of small numbers of clustered IP3Rs spaced throughout the endoplasmic reticulum. Although much emphasis has been placed on estimating the number of active Ca2+ release channels supporting Ca2+ puffs, less attention has been placed on understanding the role of cluster microarchitecture. This is important as recent data underscores the dynamic nature of IP3R transitions between heterogeneous cellular architectures and the differential behavior of IP3Rs socialized into clusters. Here, we applied a high-resolution model incorporating stochastically gating IP3Rs within a three-dimensional cytoplasmic space to demonstrate: 1), Ca2+ puffs are supported by a broad range of clustered IP3R microarchitectures; 2), cluster ultrastructure shapes Ca2+ puff characteristics; and 3), loosely corralled IP3R clusters (>200 nm interchannel separation) fail to coordinate Ca2+ puffs, owing to inefficient triggering and impaired coupling due to reduced Ca2+-induced Ca2+ release microwave velocity (<10 nm/s) throughout the channel array. Dynamic microarchitectural considerations may therefore influence Ca2+ puff occurrence/properties in intact cells, contrasting with a more minimal role for channel number over the same simulated conditions in shaping local Ca 2+ dynamics.

Original languageEnglish (US)
Pages (from-to)822-831
Number of pages10
JournalBiophysical journal
Issue number4
StatePublished - Feb 16 2011

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health under grant No. GM088790 (to J.S.M.).


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