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dc.creatorFARRELL,EMILY F
dc.creatorANTARAMIAN,ANAID
dc.creatorBENKUSKY,NANCY
dc.creatorZHU,XINSHENG
dc.creatorRUEDA,ANGÉLICA
dc.creatorGÓMEZ,ANA M
dc.creatorVALDIVIA,HÉCTOR H
dc.date2004-01-01
dc.date.accessioned2020-02-17T15:35:43Z
dc.date.available2020-02-17T15:35:43Z
dc.identifierhttps://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400015
dc.identifier.urihttps://revistaschilenas.uchile.cl/handle/2250/132046
dc.descriptionActivation 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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dc.languageen
dc.publisherSociedad de Biología de Chile
dc.relation10.4067/S0716-97602004000400015
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourceBiological Research v.37 n.4 2004
dc.subjectSorcin
dc.subjectryanodine receptors
dc.subjectCICR
dc.subjectdihydropyridine receptor
dc.subjectsarcoplasmic reticulum
dc.titleRegulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors


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