Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors
Biol. Res
;
37(4): 609-612, 2004. ilus
Article
in English
| LILACS
| ID: lil-437515
ABSTRACT
Activation of Ca2+ release channels/ryanodine receptors (RyR) by the inward Ca2+ current (ICa) 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 ICa-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 ICa, 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 ICa-triggered RyR activity and may play a role in helping terminate the positive feedback loop of CICR.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Sarcoplasmic Reticulum
/
Calcium-Binding Proteins
/
Ryanodine Receptor Calcium Release Channel
/
Myocytes, Cardiac
/
Myocardial Contraction
Limits:
Animals
Language:
English
Journal:
Biol. Res
Journal subject:
Biology
Year:
2004
Type:
Article
Affiliation country:
France
/
United States
Institution/Affiliation country:
INSERM/FR
/
University of Wisconsin Medical School/US
Similar
MEDLINE
...
LILACS
LIS