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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Autor principal:	FRIEL,DAVID
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2004
Materias:	dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400024
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spelling	oai:scielo:S0716-976020040004000242005-06-02Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamicsFRIEL,DAVID dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors 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 largerinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.37 n.4 20042004-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400024en10.4067/S0716-97602004000400024
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors
spellingShingle	dynamics sympathetic neurons endoplasmic reticulum ryanodine receptors FRIEL,DAVID Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics
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
author	FRIEL,DAVID
author_facet	FRIEL,DAVID
author_sort	FRIEL,DAVID
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	Sociedad de Biología de Chile
publishDate	2004
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400024
work_keys_str_mv	AT frieldavid interplaybetweenerca2uptakeandreleasefluxesinneuronsanditsimpactonca2dynamics
_version_	1718441378424291328

Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics

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