Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor.
نویسندگان
چکیده
The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Using site-directed mutagenesis, we identified the specific Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation site on recombinant RyR2, distinct from the site for protein kinase A (PKA) that mediates the "fight-or-flight" stress response. CaMKII phosphorylation increased RyR2 Ca2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca2+-induced Ca2+ release. Moreover, rate-dependent CaMKII phosphorylation of RyR2 was defective in heart failure. CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org.
منابع مشابه
Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the balance right.
Phosphorylation of the cardiac ryanodine receptor (RyR2) is a key mechanism regulating sarcoplasmic reticulum (SR) Ca2+ release. Differences in opinion have arisen over the importance assigned to specific phosphorylation sites on RyR2, over the kinase (s) suggested to directly phosphorylate RyR2 and surrounding the possibility that altered phosphorylation of RyR2 is associated with contractile ...
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Cardiac ryanodine receptors (RyR2s) play a critical role in excitation-contraction coupling by providing a pathway for the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol. RyR2s exist as macromolecular complexes that are regulated via binding of Ca(2+) and protein phosphorylation/dephosphorylation. The present study examined the association of endogenous CaMKII (calcium/calmo...
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ورودعنوان ژورنال:
- Circulation research
دوره 94 6 شماره
صفحات -
تاریخ انتشار 2004