A dilated cardiomyopathy mutation blunts adrenergic response and induces contractile dysfunction under chronic angiotensin II stress

In vitro, dilated cardiomyopathy (DCM)-causing mutations abolish the change in myofilament Ca2+ sensitivity when troponin I is phosphorylated by PKA. With the use of a mouse model of DCM, we show that this leads to a blunting of the response to dobutamine and under chronic ANG II stress, predisposes to systolic dysfunction characteristic of DCM.