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Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle
Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) occurs in smooth muscle as spontaneous SR Ca(2+) release or Ca(2+) sparks and, in some spiking tissues, as Ca(2+) release that is triggered by the activation of sarcolemmal Ca(2+) channels. Both processes display spatial local...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151500/ https://www.ncbi.nlm.nih.gov/pubmed/16505145 http://dx.doi.org/10.1085/jgp.200509422 |
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author | Ji, Guangju Feldman, Morris Doran, Robert Zipfel, Warren Kotlikoff, Michael I. |
author_facet | Ji, Guangju Feldman, Morris Doran, Robert Zipfel, Warren Kotlikoff, Michael I. |
author_sort | Ji, Guangju |
collection | PubMed |
description | Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) occurs in smooth muscle as spontaneous SR Ca(2+) release or Ca(2+) sparks and, in some spiking tissues, as Ca(2+) release that is triggered by the activation of sarcolemmal Ca(2+) channels. Both processes display spatial localization in that release occurs at a higher frequency at specific subcellular regions. We have used two-photon flash photolysis (TPFP) of caged Ca(2+) (DMNP-EDTA) in Fluo-4–loaded urinary bladder smooth muscle cells to determine the extent to which spatially localized increases in Ca(2+) activate SR release and to further understand the molecular and biophysical processes underlying CICR. TPFP resulted in localized Ca(2+) release in the form of Ca(2+) sparks and Ca(2+) waves that were distinguishable from increases in Ca(2+) associated with Ca(2+) uncaging, unequivocally demonstrating that Ca(2+) release occurs subsequent to a localized rise in [Ca(2+)](i). TPFP-triggered Ca(2+) release was not constrained to a few discharge regions but could be activated at all areas of the cell, with release usually occurring at or within several microns of the site of photolysis. As expected, the process of CICR was dominated by ryanodine receptor (RYR) activity, as ryanodine abolished individual Ca(2+) sparks and evoked release with different threshold and kinetics in FKBP12.6-null cells. However, TPFP CICR was not completely inhibited by ryanodine; Ca(2+) release with distinct kinetic features occurred with a higher TPFP threshold in the presence of ryanodine. This high threshold release was blocked by xestospongin C, and the pharmacological sensitivity and kinetics were consistent with CICR release at high local [Ca(2+)](i) through inositol trisphosphate (InsP(3)) receptors (InsP(3)Rs). We conclude that CICR activated by localized Ca(2+) release bears essential similarities to those observed by the activation of I(Ca) (i.e., major dependence on the type 2 RYR), that the release is not spatially constrained to a few specific subcellular regions, and that Ca(2+) release through InsP(3)R can occur at high local [Ca(2+)](i). |
format | Text |
id | pubmed-2151500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21515002008-01-17 Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle Ji, Guangju Feldman, Morris Doran, Robert Zipfel, Warren Kotlikoff, Michael I. J Gen Physiol Articles Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) occurs in smooth muscle as spontaneous SR Ca(2+) release or Ca(2+) sparks and, in some spiking tissues, as Ca(2+) release that is triggered by the activation of sarcolemmal Ca(2+) channels. Both processes display spatial localization in that release occurs at a higher frequency at specific subcellular regions. We have used two-photon flash photolysis (TPFP) of caged Ca(2+) (DMNP-EDTA) in Fluo-4–loaded urinary bladder smooth muscle cells to determine the extent to which spatially localized increases in Ca(2+) activate SR release and to further understand the molecular and biophysical processes underlying CICR. TPFP resulted in localized Ca(2+) release in the form of Ca(2+) sparks and Ca(2+) waves that were distinguishable from increases in Ca(2+) associated with Ca(2+) uncaging, unequivocally demonstrating that Ca(2+) release occurs subsequent to a localized rise in [Ca(2+)](i). TPFP-triggered Ca(2+) release was not constrained to a few discharge regions but could be activated at all areas of the cell, with release usually occurring at or within several microns of the site of photolysis. As expected, the process of CICR was dominated by ryanodine receptor (RYR) activity, as ryanodine abolished individual Ca(2+) sparks and evoked release with different threshold and kinetics in FKBP12.6-null cells. However, TPFP CICR was not completely inhibited by ryanodine; Ca(2+) release with distinct kinetic features occurred with a higher TPFP threshold in the presence of ryanodine. This high threshold release was blocked by xestospongin C, and the pharmacological sensitivity and kinetics were consistent with CICR release at high local [Ca(2+)](i) through inositol trisphosphate (InsP(3)) receptors (InsP(3)Rs). We conclude that CICR activated by localized Ca(2+) release bears essential similarities to those observed by the activation of I(Ca) (i.e., major dependence on the type 2 RYR), that the release is not spatially constrained to a few specific subcellular regions, and that Ca(2+) release through InsP(3)R can occur at high local [Ca(2+)](i). The Rockefeller University Press 2006-03 /pmc/articles/PMC2151500/ /pubmed/16505145 http://dx.doi.org/10.1085/jgp.200509422 Text en Copyright © 2006, The Rockefeller University Press 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 | Articles Ji, Guangju Feldman, Morris Doran, Robert Zipfel, Warren Kotlikoff, Michael I. Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title | Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title_full | Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title_fullStr | Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title_full_unstemmed | Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title_short | Ca(2+)-Induced Ca(2+) Release through Localized Ca(2+) Uncaging in Smooth Muscle |
title_sort | ca(2+)-induced ca(2+) release through localized ca(2+) uncaging in smooth muscle |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151500/ https://www.ncbi.nlm.nih.gov/pubmed/16505145 http://dx.doi.org/10.1085/jgp.200509422 |
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