No Contribution of IP3-R(2) to Disease Phenotype in Models of Dilated Cardiomyopathy or Pressure Overload Hypertrophy

We investigated the contribution of inositol(1,4,5)-trisphosphate (Ins(1,4,5)P3IP3) receptors (IP3-R) to disease progression in mouse models of dilated cardiomyopathy (DCM) and pressure overload hypertrophy. Mice expressing mammalian sterile 20–like kinase and dominant-negative phosphatidylinositol-3-kinase in heart (Mst1×dn-PI3K-2Tg; DCM-2Tg) develop severe DCM and conduction block, associated with increased expression of type 2 IP3-R (IP3-R(2)) and heightened generation of Ins(1,4,5)P3. Similar increases in Ins(1,4,5)P3and IP3-R(2) are caused by transverse aortic constriction.