Abstract：
:In the heart, Ca(2+) released from the intracellular Ca(2+) storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca(2+) release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, including FKBP12.6, calsequestrin (CASQ2), triadin (TRD) and junctin (JN). Acquired and genetic defects in the components of the release channel complex result in a spectrum of abnormal Ca(2+) release phenotypes ranging from arrhythmogenic spontaneous Ca(2+) releases and Ca(2+) alternans to the uniformly diminished systolic Ca(2+) release characteristic of heart failure. In this article, we will present an overview of the structure and molecular components of the SR and Ca(2+) release machinery and its modulation by different intracellular factors, such as Ca(2+) levels inside the SR as well as phosphorylation and redox modification of RyR2s. We will also discuss the relationships between abnormal SR Ca(2+) release and various cardiac disease phenotypes, including, arrhythmias and heart failure, and consider SR Ca(2+) release as a potential therapeutic target.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Györke S,Carnes Cdoi
10.1016/j.pharmthera.2008.06.002subject
Has Abstractpub_date
2008-09-01 00:00:00pages
340-54issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(08)00120-4journal_volume
119pub_type
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