| Registro completo |
| Provedor de dados: |
Biol. Res.
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| País: |
Chile
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| Título: |
Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
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| Autores: |
FARRELL,EMILY F
ANTARAMIAN,ANAID
BENKUSKY,NANCY
ZHU,XINSHENG
RUEDA,ANGÉLICA
GÓMEZ,ANA M
VALDIVIA,HÉCTOR H
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| Data: |
2004-01-01
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| Ano: |
2004
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| Palavras-chave: |
Sorcin
Ryanodine receptors
CICR
Dihydropyridine receptor
Sarcoplasmic reticulum
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| Resumo: |
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.
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| Tipo: |
Journal article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400015
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| Editor: |
Sociedad de Biología de Chile
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| Formato: |
text/html
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| Fonte: |
Biological Research v.37 n.4 2004
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