Targeted inactivation of Gαi does not alter cardiac function or β-adrenergic sensitivity

Inhibitory G alpha (i) protein increases in the myocardium during hypertrophy and has been associated with beta -adrenergic receptor (beta -AR) desensitization, contractile dysfunction, and progression of cardiac disease. The role of G alpha (i) proteins in mediating basal cardiac function and beta -AR response in nonpathological myocardium, however, is uncertain. Transgenic mice with targeted inactivation of G alpha (i2) or G alpha (i3) were examined for in vivo cardiac function with the use of conscious echocardiography and for ex vivo cardiac response to inotropic stimulation with the use of Langendorff blood-perfused isolated hearts and adult ventricular cardiomyocytes. Echocardiography revealed that percent fractional shortening and heart rate were similar among wild-type, G alpha (i2)-null, and G alpha (i3)-null mice. Comparable baseline diastolic and contractile performance was also observed in isolated hearts and isolated ventricular myocytes from wild-type mice and mice lacking G alpha (i) proteins. Isoproterenol infusion enhanced diastolic and contractile performance to a similar degree in wild-type, G alpha (i2)-null, and G alpha (i3)-null mice. These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac function or sensitivity to beta -AR stimulation in nonpathological myocardium.