Calsequestrin determines the functional size and stability of cardiac intracellular calcium stores: Mechanism for hereditary arrhythmia
Calsequestrin
Cardiac muscle
Calcium in biology
DOI:
10.1073/pnas.1932318100
Publication Date:
2003-10-01T19:44:34Z
AUTHORS (6)
ABSTRACT
Calsequestrin is a high-capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR), an intracellular Ca release and storage organelle in muscle. Mutations cardiac calsequestrin gene ( CSQ2 ) have been linked to arrhythmias sudden death. We used Ca-imaging patch-clamp methods combination with adenoviral transfer strategies explore function of adult rat heart cells. By increasing or decreasing levels, we showed that not only determines capacity SR but also positively controls amount released from this during excitation–contraction coupling. by prolonging duration fluxes through Ca-release sites. In addition, dynamics functional restitution sites after discharge were prolonged when levels elevated accelerated presence lowered levels. Furthermore, profound disturbances rhythmic transients myocytes undergoing periodic electrical stimulation observed reduced. conclude key determinant size stability stores appears exert its effects influencing local luminal concentration-dependent gating channels acting as both reservoir sink for SR. The abnormal reduced provides plausible explanation ventricular arrhythmia associated mutations .
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