MYOCARDIAL BETA-ADRENERGIC-RECEPTOR SIGNALING IN-VIVO - INSIGHTS FROMTRANSGENIC MICE

Heart failure is a problem of increasing importance in cardiovascular medicine. An important characteristic of heart failure is reduced agon ist-stimulated adenylyl cyclase activity (receptor desensitization) du e to both diminished receptor number (receptor downregulation) and imp aired receptor function (receptor uncoupling). These changes in the -a drenergic receptor (-AR) system may in part account for some of the ab normalities of contractile function in this disease. Myocardial contra ction is closely regulated by G protein coupled beta-adrenergic recept ors through the action of the second messenger cAMP. The beta-adrenerg ic receptors themselves are regulated by a set of specific kinases, te rmed the G-protein-coupled receptor kinases. The study of this complex system in vive has recently been advanced by the development of trans genic and gene targeted (''knock-out'') mouse models. Combining transg enic technology with sophisticated physiological measurements of cardi ac hemodynamics is an extremely powerful strategy to study the regulat ion of myocardial contractility in the normal and failing heart.