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Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating
Cytosolic calcium concentration in resting cardiac myocytes locally fluctuates as a result of spontaneous microscopic Ca(2+) releases or abruptly rises as a result of an external trigger. These processes, observed as calcium sparks, are fundamental for proper function of cardiac muscle. In this stud...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894546/ https://www.ncbi.nlm.nih.gov/pubmed/20548054 http://dx.doi.org/10.1085/jgp.200910380 |
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author | Zahradníková, Alexandra Valent, Ivan Zahradník, Ivan |
author_facet | Zahradníková, Alexandra Valent, Ivan Zahradník, Ivan |
author_sort | Zahradníková, Alexandra |
collection | PubMed |
description | Cytosolic calcium concentration in resting cardiac myocytes locally fluctuates as a result of spontaneous microscopic Ca(2+) releases or abruptly rises as a result of an external trigger. These processes, observed as calcium sparks, are fundamental for proper function of cardiac muscle. In this study, we analyze how the characteristics of spontaneous and triggered calcium sparks are related to cardiac ryanodine receptor (RYR) gating. We show that the frequency of spontaneous sparks and the probability distribution of calcium release flux quanta of triggered sparks correspond quantitatively to predictions of an allosteric homotetrameric model of RYR gating. This model includes competitive binding of Ca(2+) and Mg(2+) ions to the RYR activation sites and allosteric interaction between divalent ion binding and channel opening. It turns out that at rest, RYRs are almost fully occupied by Mg(2+). Therefore, spontaneous sparks are most frequently evoked by random openings of the highly populated but rarely opening Mg(4)RYR and CaMg(3)RYR forms, whereas triggered sparks are most frequently evoked by random openings of the less populated but much more readily opening Ca(2)Mg(2)RYR and Ca(3)MgRYR forms. In both the spontaneous and the triggered sparks, only a small fraction of RYRs in the calcium release unit manages to open during the spark because of the limited rate of Mg(2+) unbinding. This mechanism clarifies the unexpectedly low calcium release flux during elementary release events and unifies the theory of calcium signaling in resting and contracting cardiac myocytes. |
format | Text |
id | pubmed-2894546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28945462011-01-01 Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating Zahradníková, Alexandra Valent, Ivan Zahradník, Ivan J Gen Physiol Article Cytosolic calcium concentration in resting cardiac myocytes locally fluctuates as a result of spontaneous microscopic Ca(2+) releases or abruptly rises as a result of an external trigger. These processes, observed as calcium sparks, are fundamental for proper function of cardiac muscle. In this study, we analyze how the characteristics of spontaneous and triggered calcium sparks are related to cardiac ryanodine receptor (RYR) gating. We show that the frequency of spontaneous sparks and the probability distribution of calcium release flux quanta of triggered sparks correspond quantitatively to predictions of an allosteric homotetrameric model of RYR gating. This model includes competitive binding of Ca(2+) and Mg(2+) ions to the RYR activation sites and allosteric interaction between divalent ion binding and channel opening. It turns out that at rest, RYRs are almost fully occupied by Mg(2+). Therefore, spontaneous sparks are most frequently evoked by random openings of the highly populated but rarely opening Mg(4)RYR and CaMg(3)RYR forms, whereas triggered sparks are most frequently evoked by random openings of the less populated but much more readily opening Ca(2)Mg(2)RYR and Ca(3)MgRYR forms. In both the spontaneous and the triggered sparks, only a small fraction of RYRs in the calcium release unit manages to open during the spark because of the limited rate of Mg(2+) unbinding. This mechanism clarifies the unexpectedly low calcium release flux during elementary release events and unifies the theory of calcium signaling in resting and contracting cardiac myocytes. The Rockefeller University Press 2010-07 /pmc/articles/PMC2894546/ /pubmed/20548054 http://dx.doi.org/10.1085/jgp.200910380 Text en © 2010 Zahradníková et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Zahradníková, Alexandra Valent, Ivan Zahradník, Ivan Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title | Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title_full | Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title_fullStr | Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title_full_unstemmed | Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title_short | Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating |
title_sort | frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to ryr gating |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894546/ https://www.ncbi.nlm.nih.gov/pubmed/20548054 http://dx.doi.org/10.1085/jgp.200910380 |
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