REGULATION OF MYOCARDIAL-CONTRACTILITY - INSIGHTS FROM TRANSGENIC MICE

Myocardial contraction occurs when calcium (Ca2+) is released from the sarcoplasmic reticulum, binding troponin C and allowing actin and myo sin to cross link. Ca2+ release and uptake is closely regulated by G p rotein-coupled beta-adrenergic receptors through the action of the sec ond messenger cAMP. An increase in cAMP level leads to phosphorylation of key regulatory proteins affecting intracellular Ca2+ homeostasis. The beta-adrenergic receptors themselves ave regulated by a set of spe cific kinases, termed the G-protein-coupled receptor kinases (GRKs). T he study of this complex system in vivo has recently been advanced by the development of transgenic and gene-targeted (knockout) mouse model s. Combining transgenic technology with sophisticated physiological me asurements of cardiac hemodynamics is an extremely powerful approach t o the study of myocardial contractility and its regulation. This revie w focuses on several recent transgenic mouse models that have increase d our understanding of the regulation of cardiac contractility.