Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics
In neurons, depolarizing stimuli open voltage-gated Ca2+ channels, leading to Ca2+ entry and a rise in the cytoplasmic free Ca2+ concentration ([Ca2+]i). While such [Ca2+]i elevations are initiated by Ca2+ entry, they are also influenced by Ca2+ transporting organelles such as mitochondria and the e...
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doaj-c33301a0b299439eba7bc8e1bf8af3132020-11-24T21:00:18ZengBMCBiological Research0716-97600717-62872004-01-01374665674Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamicsDAVID FRIELIn neurons, depolarizing stimuli open voltage-gated Ca2+ channels, leading to Ca2+ entry and a rise in the cytoplasmic free Ca2+ concentration ([Ca2+]i). While such [Ca2+]i elevations are initiated by Ca2+ entry, they are also influenced by Ca2+ transporting organelles such as mitochondria and the endoplasmic reticulum (ER). This review summarizes contributions from the ER to depolarization-evoked [Ca2+]i responses in sympathetic neurons. As in other neurons, ER Ca2+ uptake depends on SERCAs, while passive Ca2+ release depends on ryanodine receptors (RyRs). RyRs are Ca2+ permeable channels that open in response to increases in [Ca2+]i, thereby permitting [Ca2+]i elevations to trigger Ca2+ release through Ca2+-induced Ca2+ release (CICR). However, whether this leads to net Ca2+ release from the ER critically depends upon the relative rates of Ca2+ uptake and release. We found that when RyRs are sensitized with caffeine, small evoked [Ca2+]i elevations do trigger net Ca2+ release, but in the absence of caffeine, net Ca2+ uptake occurs, indicating that Ca2+ uptake is stronger than Ca2+ release under these conditions. Nevertheless, by increasing ER Ca2+ permeability, RyRs reduce the strength of Ca2+ buffering by the ER in a [Ca2+]I-dependent manner, providing a novel mechanism for [Ca2+]i response acceleration. Analysis of the underlying Ca2+ fluxes provides an explanation of this and two other modes of CICR that are revealed as [Ca2+]i elevations become progressively largerhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400024dynamicssympathetic neuronsendoplasmic reticulumryanodine receptors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
DAVID FRIEL |
spellingShingle |
DAVID FRIEL Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics Biological Research dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors |
author_facet |
DAVID FRIEL |
author_sort |
DAVID FRIEL |
title |
Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics |
title_short |
Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics |
title_full |
Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics |
title_fullStr |
Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics |
title_full_unstemmed |
Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics |
title_sort |
interplay between er ca2+ uptake and release fluxes in neurons and its impact on [ca2+] dynamics |
publisher |
BMC |
series |
Biological Research |
issn |
0716-9760 0717-6287 |
publishDate |
2004-01-01 |
description |
In neurons, depolarizing stimuli open voltage-gated Ca2+ channels, leading to Ca2+ entry and a rise in the cytoplasmic free Ca2+ concentration ([Ca2+]i). While such [Ca2+]i elevations are initiated by Ca2+ entry, they are also influenced by Ca2+ transporting organelles such as mitochondria and the endoplasmic reticulum (ER). This review summarizes contributions from the ER to depolarization-evoked [Ca2+]i responses in sympathetic neurons. As in other neurons, ER Ca2+ uptake depends on SERCAs, while passive Ca2+ release depends on ryanodine receptors (RyRs). RyRs are Ca2+ permeable channels that open in response to increases in [Ca2+]i, thereby permitting [Ca2+]i elevations to trigger Ca2+ release through Ca2+-induced Ca2+ release (CICR). However, whether this leads to net Ca2+ release from the ER critically depends upon the relative rates of Ca2+ uptake and release. We found that when RyRs are sensitized with caffeine, small evoked [Ca2+]i elevations do trigger net Ca2+ release, but in the absence of caffeine, net Ca2+ uptake occurs, indicating that Ca2+ uptake is stronger than Ca2+ release under these conditions. Nevertheless, by increasing ER Ca2+ permeability, RyRs reduce the strength of Ca2+ buffering by the ER in a [Ca2+]I-dependent manner, providing a novel mechanism for [Ca2+]i response acceleration. Analysis of the underlying Ca2+ fluxes provides an explanation of this and two other modes of CICR that are revealed as [Ca2+]i elevations become progressively larger |
topic |
dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors |
url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400024 |
work_keys_str_mv |
AT davidfriel interplaybetweenerca2uptakeandreleasefluxesinneuronsanditsimpactonca2dynamics |
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1716780271511011328 |