dc.creator | FARRELL,EMILY F | |
dc.creator | ANTARAMIAN,ANAID | |
dc.creator | BENKUSKY,NANCY | |
dc.creator | ZHU,XINSHENG | |
dc.creator | RUEDA,ANGÉLICA | |
dc.creator | GÓMEZ,ANA M | |
dc.creator | VALDIVIA,HÉCTOR H | |
dc.date | 2004-01-01 | |
dc.date.accessioned | 2020-02-17T15:35:43Z | |
dc.date.available | 2020-02-17T15:35:43Z | |
dc.identifier | https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400015 | |
dc.identifier.uri | https://revistaschilenas.uchile.cl/handle/2250/132046 | |
dc.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. | |
dc.format | text/html | |
dc.language | en | |
dc.publisher | Sociedad de Biología de Chile | |
dc.relation | 10.4067/S0716-97602004000400015 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.source | Biological Research v.37 n.4 2004 | |
dc.subject | Sorcin | |
dc.subject | ryanodine receptors | |
dc.subject | CICR | |
dc.subject | dihydropyridine receptor | |
dc.subject | sarcoplasmic reticulum | |
dc.title | Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors | |