Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors

Activation of Ca2+ release channels/ryanodine receptors (RyR) by the inward Ca2+ current (I Ca) gives rise to Ca2+-induced Ca2+ release (CICR), the amplifying Ca2+ signaling mechanism that triggers contraction of the heart. CICR, in theory, is a high-gain, self-regenerating process, but an unidentif...

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Autores principales:	FARRELL,EMILY F, ANTARAMIAN,ANAID, BENKUSKY,NANCY, ZHU,XINSHENG, RUEDA,ANGÉLICA, GÓMEZ,ANA M, VALDIVIA,HÉCTOR H
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2004
Materias:	Sorcin ryanodine receptors CICR dihydropyridine receptor sarcoplasmic reticulum
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400015
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spelling	oai:scielo:S0716-976020040004000152005-06-02Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptorsFARRELL,EMILY FANTARAMIAN,ANAIDBENKUSKY,NANCYZHU,XINSHENGRUEDA,ANGÉLICAGÓMEZ,ANA MVALDIVIA,HÉCTOR H Sorcin ryanodine receptors CICR dihydropyridine receptor sarcoplasmic reticulum Activation of Ca2+ release channels/ryanodine receptors (RyR) by the inward Ca2+ current (I Ca) gives rise to Ca2+-induced Ca2+ release (CICR), the amplifying Ca2+ signaling mechanism that triggers contraction of the heart. CICR, in theory, is a high-gain, self-regenerating process, but an unidentified mechanism stabilizes it in vivo. Sorcin, a 21.6 kDa Ca2+-binding protein, binds to cardiac RyRs with high affinity and completely inhibits channel activity. Sorcin significantly inhibits both the spontaneous activity of RyRs in quiescent cells (visualized as Ca2+ sparks) and the I Ca-triggered activity of RyRs that gives rise to [Ca2+]i transients. Since sorcin decreases the amplitude of the [Ca2+]i transient without affecting the amplitude of I Ca, the overall effect of sorcin is to reduce the "gain" of excitation-contraction coupling. Immunocytochemical staining shows that sorcin localizes to the dyadic space of ventricular cardiac myocytes. Ca2+ induces conformational changes and promotes translocation of sorcin between soluble and membranous compartments, but the [Ca2+] required for the latter process (ED50 = ~200 mM) appears to be reached only within the dyadic space. Thus, sorcin is a potent inhibitor of both spontaneous and I Ca-triggered RyR activity and may play a role in helping terminate the positive feedback loop of CICR.info: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=S0716-97602004000400015en10.4067/S0716-97602004000400015
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Sorcin ryanodine receptors CICR dihydropyridine receptor sarcoplasmic reticulum
spellingShingle	Sorcin ryanodine receptors CICR dihydropyridine receptor sarcoplasmic reticulum FARRELL,EMILY F ANTARAMIAN,ANAID BENKUSKY,NANCY ZHU,XINSHENG RUEDA,ANGÉLICA GÓMEZ,ANA M VALDIVIA,HÉCTOR H Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
description	Activation of Ca2+ release channels/ryanodine receptors (RyR) by the inward Ca2+ current (I Ca) gives rise to Ca2+-induced Ca2+ release (CICR), the amplifying Ca2+ signaling mechanism that triggers contraction of the heart. CICR, in theory, is a high-gain, self-regenerating process, but an unidentified mechanism stabilizes it in vivo. Sorcin, a 21.6 kDa Ca2+-binding protein, binds to cardiac RyRs with high affinity and completely inhibits channel activity. Sorcin significantly inhibits both the spontaneous activity of RyRs in quiescent cells (visualized as Ca2+ sparks) and the I Ca-triggered activity of RyRs that gives rise to [Ca2+]i transients. Since sorcin decreases the amplitude of the [Ca2+]i transient without affecting the amplitude of I Ca, the overall effect of sorcin is to reduce the "gain" of excitation-contraction coupling. Immunocytochemical staining shows that sorcin localizes to the dyadic space of ventricular cardiac myocytes. Ca2+ induces conformational changes and promotes translocation of sorcin between soluble and membranous compartments, but the [Ca2+] required for the latter process (ED50 = ~200 mM) appears to be reached only within the dyadic space. Thus, sorcin is a potent inhibitor of both spontaneous and I Ca-triggered RyR activity and may play a role in helping terminate the positive feedback loop of CICR.
author	FARRELL,EMILY F ANTARAMIAN,ANAID BENKUSKY,NANCY ZHU,XINSHENG RUEDA,ANGÉLICA GÓMEZ,ANA M VALDIVIA,HÉCTOR H
author_facet	FARRELL,EMILY F ANTARAMIAN,ANAID BENKUSKY,NANCY ZHU,XINSHENG RUEDA,ANGÉLICA GÓMEZ,ANA M VALDIVIA,HÉCTOR H
author_sort	FARRELL,EMILY F
title	Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
title_short	Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
title_full	Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
title_fullStr	Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
title_full_unstemmed	Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
title_sort	regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
publisher	Sociedad de Biología de Chile
publishDate	2004
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400015
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Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors

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