Targeted inactivation of G alpha(i) does not alter cardiac function or beta-adrenergic sensitivity

Inhibitory G alpha (i) protein increases in the myocardium during hypertrop hy and has been associated with beta -adrenergic receptor (beta -AR) desens itization, 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. Transgen ic mice with targeted inactivation of G alpha (i2) or G alpha (i3) were exa mined for in vivo cardiac function with the use of conscious echocardiograp hy and for ex vivo cardiac response to inotropic stimulation with the use o f Langendorff blood-perfused isolated hearts and adult ventricular cardiomy ocytes. Echocardiography revealed that percent fractional shortening and he art rate were similar among wild-type, G alpha (i2)-null, and G alpha (i3)- null mice. Comparable baseline diastolic and contractile performance was al so observed in isolated hearts and isolated ventricular myocytes from wild- type mice and mice lacking G alpha (i) proteins. Isoproterenol infusion enh anced diastolic and contractile performance to a similar degree in wild-typ e, G alpha (i2)-null, and G alpha (i3)-null mice. These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac funct ion or sensitivity to beta -AR stimulation in nonpathological myocardium.