Alternations of ryanodine receptor type 2 (RyR-2) associate with cardiac hypertrophy and dysfunction, but the mechanism remains elusive. We here examined this by using the mice with heterozygous reduction of
RyR-2
gene (
RyR-2
+/−
) and their littermate wild type ones (
RyR-2
+
/
+
). The mutation induced an impairing of Ca
2+
release from sarcoplasmic reticulum (SR) but did not affect growth and morphology of the cardiomyocytes at basal condition. When pressure overload was imposed, comparing to
RyR-2
+
/
+
mice, the
RyR-2
+/−
mice displayed an attenuated cardiac hypertrophy and contractibility, the increased death of cardiomyocytes, further down-regulated expression of
RyR-2
, the different reprogramming of SR Ca
2+
-ATPase 2, L-type Ca
2+
channel and Na
1+
/Ca
2+
exchanger expressions, and a unchanged vasculature reduction in the heart at 3 weeks. Additionally, the decrease of binding of FKBP12.6 to RyR-2 and the increase in phosphorylation of RyR-2 by protein kinase A were aggravated in the loaded
RyR-2
+/−
heart. Furthermore, activation of protein kinase B/Akt and calcineurin by pressure overload was declined whereas that of Ca
2+
/calmudulin-dependent protein kinase II unchanged in the
RyR-2
+/−
heart comparing the
RyR-2
+
/
+
one. These results suggest that reduction of RyR-2 attenuated cardiac hypertrophy but accelerated the development of cardiac dysfunctions through disturbed Ca
2+
homeostasis, impaired activation of Akt and calcineurin and increased cardiomyocyte death during pressure overload.
Ryanodine Receptor Type 2 Is Required for the Development of Pressure Overload-Induced Cardiac Hypertrophy
