Abnormal contraction caused by expression of Gi-coupled receptor in transgenic model of dilated cardiomyopathy

Departments of Radiology, 1 Medicine, 2 and Pharmacology, 3 Cardiovascular Research Institute, 4 and Gladstone Institute of Cardiovascular Disease, 5 University of California, San Francisco, California 94143 Although increased G i signaling has been associated with dilated cardiomyopathy in humans, its role is not clear. Our goal was to determine the effects of chronically increased G i signaling on myocardial function. We studied transgenic mice that expressed a G i -coupled receptor (Ro1) that was targeted to the heart and regulated by a tetracycline-controlled expression system. Ro1 expression for 8 wk resulted in abnormal contractions of right ventricular muscle strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 ± 3 to 13 ± 2 mN/mm 2 , P