Chen, "Abnormal termination of [Ca.sup.2+] release is a common defect of
RyR2 mutations associated with cardiomyopathies," Circulation Research, vol.
RyR2 channels are found in sarcoplasmic reticulum and have important roles in cardiac myocyte contraction and the generation of autorhythmicity in SAN cells [51].
Previous studies have shown that hypertension and HF promote serious dysfunctions that may affect the CRUs, including orphaned
RyR2, loss of the RyR2-FKBP12.6 interaction (7) and dyssynchronous [Ca.sup.2+] sparks (8).
Interestingly, RyR1 siRNA and
RyR2 siRNA were equally effective in blocking the dendrite-promoting activity of PCB-95.
Calcium regulatory proteins are mainly composed of L-type Ca[sup]2+ channels (LTCCs), ryanodine receptor 2 (
RyR2), and Na[sup]+/Ca[sup]2+ exchanger (NCX).
A subset of slice cultures was simultaneously transfected with siRNA (small interfering RNA) specific for RyR1 or
RyR2. Slice cultures were exposed to vehicle, and PCBs were added to the culture medium during 4-6 DIV.
Three different isoforms of ryanodine receptors are known: ryanodine receptor type 1 (RyR1; [5] OMIM 180901) and type 2 (
RyR2; OMIM 180902) are produced in skeletal and cardiac muscle, respectively, whereas ryanodine receptor type 3 (RyR3; OMIM 180903) is produced in a wide range of tissue.
For example, a recent study revealed that expressions of 630 genes in early hypoxia were regulated by ROS, including p65, NF-?B, Ca [sup]2+-handling proteins, such as calsequestrin, CAM, and calreticulin, and ion channels, including NCX, Na [sup]+-K [sup]+-ATPase, SERCA2a, and PLB; as well as the stress markers, such as
RyR2, ANP, and BNP.[sup][14],[15],[16]