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Mitochondrial Participation in the Intracellular Ca(2+) Network

Calcium can activate mitochondrial metabolism, and the possibility that mitochondrial Ca(2+) uptake and extrusion modulate free cytosolic [Ca(2+)] (Ca(c)) now has renewed interest. We use whole-cell and perforated patch clamp methods together with rapid local perfusion to introduce probes and inhibi...

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Autores principales: Babcock, Donner F., Herrington, James, Goodwin, Paul C., Park, Young Bae, Hille, Bertil
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132502/
https://www.ncbi.nlm.nih.gov/pubmed/9049249
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author Babcock, Donner F.
Herrington, James
Goodwin, Paul C.
Park, Young Bae
Hille, Bertil
author_facet Babcock, Donner F.
Herrington, James
Goodwin, Paul C.
Park, Young Bae
Hille, Bertil
author_sort Babcock, Donner F.
collection PubMed
description Calcium can activate mitochondrial metabolism, and the possibility that mitochondrial Ca(2+) uptake and extrusion modulate free cytosolic [Ca(2+)] (Ca(c)) now has renewed interest. We use whole-cell and perforated patch clamp methods together with rapid local perfusion to introduce probes and inhibitors to rat chromaffin cells, to evoke Ca(2+) entry, and to monitor Ca(2+)-activated currents that report near-surface [Ca(2+)]. We show that rapid recovery from elevations of Ca(c) requires both the mitochondrial Ca(2+) uniporter and the mitochondrial energization that drives Ca(2+) uptake through it. Applying imaging and single-cell photometric methods, we find that the probe rhod-2 selectively localizes to mitochondria and uses its responses to quantify mitochondrial free [Ca(2+)] (Ca(m)). The indicated resting Ca(m) of 100–200 nM is similar to the resting Ca(c) reported by the probes indo-1 and Calcium Green, or its dextran conjugate in the cytoplasm. Simultaneous monitoring of Ca(m) and Ca(c) at high temporal resolution shows that, although Ca(m) increases less than Ca(c), mitochondrial sequestration of Ca(2+) is fast and has high capacity. We find that mitochondrial Ca(2+) uptake limits the rise and underlies the rapid decay of Ca(c) excursions produced by Ca(2+) entry or by mobilization of reticular stores. We also find that subsequent export of Ca(2+) from mitochondria, seen as declining Ca(m), prolongs complete Ca(c) recovery and that suppressing export of Ca(2+), by inhibition of the mitochondrial Na(+)/ Ca(2+) exchanger, reversibly hastens final recovery of Ca(c). We conclude that mitochondria are active participants in cellular Ca(2+) signaling, whose unique role is determined by their ability to rapidly accumulate and then release large quantities of Ca(2+).
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spelling pubmed-21325022008-05-01 Mitochondrial Participation in the Intracellular Ca(2+) Network Babcock, Donner F. Herrington, James Goodwin, Paul C. Park, Young Bae Hille, Bertil J Cell Biol Article Calcium can activate mitochondrial metabolism, and the possibility that mitochondrial Ca(2+) uptake and extrusion modulate free cytosolic [Ca(2+)] (Ca(c)) now has renewed interest. We use whole-cell and perforated patch clamp methods together with rapid local perfusion to introduce probes and inhibitors to rat chromaffin cells, to evoke Ca(2+) entry, and to monitor Ca(2+)-activated currents that report near-surface [Ca(2+)]. We show that rapid recovery from elevations of Ca(c) requires both the mitochondrial Ca(2+) uniporter and the mitochondrial energization that drives Ca(2+) uptake through it. Applying imaging and single-cell photometric methods, we find that the probe rhod-2 selectively localizes to mitochondria and uses its responses to quantify mitochondrial free [Ca(2+)] (Ca(m)). The indicated resting Ca(m) of 100–200 nM is similar to the resting Ca(c) reported by the probes indo-1 and Calcium Green, or its dextran conjugate in the cytoplasm. Simultaneous monitoring of Ca(m) and Ca(c) at high temporal resolution shows that, although Ca(m) increases less than Ca(c), mitochondrial sequestration of Ca(2+) is fast and has high capacity. We find that mitochondrial Ca(2+) uptake limits the rise and underlies the rapid decay of Ca(c) excursions produced by Ca(2+) entry or by mobilization of reticular stores. We also find that subsequent export of Ca(2+) from mitochondria, seen as declining Ca(m), prolongs complete Ca(c) recovery and that suppressing export of Ca(2+), by inhibition of the mitochondrial Na(+)/ Ca(2+) exchanger, reversibly hastens final recovery of Ca(c). We conclude that mitochondria are active participants in cellular Ca(2+) signaling, whose unique role is determined by their ability to rapidly accumulate and then release large quantities of Ca(2+). The Rockefeller University Press 1997-02-24 /pmc/articles/PMC2132502/ /pubmed/9049249 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Babcock, Donner F.
Herrington, James
Goodwin, Paul C.
Park, Young Bae
Hille, Bertil
Mitochondrial Participation in the Intracellular Ca(2+) Network
title Mitochondrial Participation in the Intracellular Ca(2+) Network
title_full Mitochondrial Participation in the Intracellular Ca(2+) Network
title_fullStr Mitochondrial Participation in the Intracellular Ca(2+) Network
title_full_unstemmed Mitochondrial Participation in the Intracellular Ca(2+) Network
title_short Mitochondrial Participation in the Intracellular Ca(2+) Network
title_sort mitochondrial participation in the intracellular ca(2+) network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132502/
https://www.ncbi.nlm.nih.gov/pubmed/9049249
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