Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3

Summary: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that link extracellular stimuli to Ca2+ signals. Ca2+ release from intracellular stores is “quantal”: low IP3 concentrations rapidly release a fraction of the stores. Ca2+ release then slows or terminates without...

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Autores principales:	Ana M. Rossi, Andrew M. Riley, Geneviève Dupont, Taufiq Rahman, Barry V.L. Potter, Colin W. Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Ca2+ signaling endoplasmic reticulum IP3 receptor partial agonist quantal Ca2+ release receptor inactivation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d8a24df4d63f46e6850a128da1909549
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spelling	oai:doaj.org-article:d8a24df4d63f46e6850a128da19095492021-11-04T04:29:21ZQuantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP32211-124710.1016/j.celrep.2021.109932https://doaj.org/article/d8a24df4d63f46e6850a128da19095492021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014054https://doaj.org/toc/2211-1247Summary: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that link extracellular stimuli to Ca2+ signals. Ca2+ release from intracellular stores is “quantal”: low IP3 concentrations rapidly release a fraction of the stores. Ca2+ release then slows or terminates without compromising responses to further IP3 additions. The mechanisms are unresolved. Here, we synthesize a high-affinity partial agonist of IP3Rs and use it to demonstrate that quantal responses do not require heterogenous Ca2+ stores. IP3Rs respond incrementally to IP3 and close after the initial response to low IP3 concentrations. Comparing functional responses with IP3 binding shows that only a tiny fraction of a cell’s IP3Rs mediate incremental Ca2+ release; inactivation does not therefore affect most IP3Rs. We conclude, and test by simulations, that Ca2+ signals evoked by IP3 pulses arise from rapid activation and then inactivation of very few IP3Rs. This allows IP3Rs to behave as increment detectors mediating graded Ca2+ release.Ana M. RossiAndrew M. RileyGeneviève DupontTaufiq RahmanBarry V.L. PotterColin W. TaylorElsevierarticleCa2+ signalingendoplasmic reticulumIP3 receptorpartial agonistquantal Ca2+ releasereceptor inactivationBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109932- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ca2+ signaling endoplasmic reticulum IP3 receptor partial agonist quantal Ca2+ release receptor inactivation Biology (General) QH301-705.5
spellingShingle	Ca2+ signaling endoplasmic reticulum IP3 receptor partial agonist quantal Ca2+ release receptor inactivation Biology (General) QH301-705.5 Ana M. Rossi Andrew M. Riley Geneviève Dupont Taufiq Rahman Barry V.L. Potter Colin W. Taylor Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
description	Summary: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that link extracellular stimuli to Ca2+ signals. Ca2+ release from intracellular stores is “quantal”: low IP3 concentrations rapidly release a fraction of the stores. Ca2+ release then slows or terminates without compromising responses to further IP3 additions. The mechanisms are unresolved. Here, we synthesize a high-affinity partial agonist of IP3Rs and use it to demonstrate that quantal responses do not require heterogenous Ca2+ stores. IP3Rs respond incrementally to IP3 and close after the initial response to low IP3 concentrations. Comparing functional responses with IP3 binding shows that only a tiny fraction of a cell’s IP3Rs mediate incremental Ca2+ release; inactivation does not therefore affect most IP3Rs. We conclude, and test by simulations, that Ca2+ signals evoked by IP3 pulses arise from rapid activation and then inactivation of very few IP3Rs. This allows IP3Rs to behave as increment detectors mediating graded Ca2+ release.
format	article
author	Ana M. Rossi Andrew M. Riley Geneviève Dupont Taufiq Rahman Barry V.L. Potter Colin W. Taylor
author_facet	Ana M. Rossi Andrew M. Riley Geneviève Dupont Taufiq Rahman Barry V.L. Potter Colin W. Taylor
author_sort	Ana M. Rossi
title	Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
title_short	Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
title_full	Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
title_fullStr	Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
title_full_unstemmed	Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3
title_sort	quantal ca2+ release mediated by very few ip3 receptors that rapidly inactivate allows graded responses to ip3
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/d8a24df4d63f46e6850a128da1909549
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Quantal Ca2+ release mediated by very few IP3 receptors that rapidly inactivate allows graded responses to IP3

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