My laboratory’s research is focused on the role of subcellular compartmentation of signaling and cellular redox state in cardiac physiology during G protein coupled receptor (GPCR) activation and during conditions of stress, such as myocardial ischemia-reperfusion. Specific interests include determining the role of protein kinase (PKC and mitogen activated protein kinases (MAPK)) and protein phosphatase mediated actions in myocardial membrane and mitochondrial fractions. The membrane compartment is further characterized by isolating lipid rafts and caveolae. Caveolae are flask shaped invaginations of the plasma membrane that are enriched in cholesterol and the scaffolding protein caveolin. Numerous second messengers have been shown to be concentrated in or traffic through caveolae in multiple cell types. Studies in large (porcine) and small animal (rat) in vivo preparations and isolated perfused rat hearts focus on subcellular signaling and regulation of ventricular function and myocardial infarction. These studies are complemented by determining the effects of subcellular signaling on contractility, intracellular calcium homeostasis, redox state, and mitochondrial function in isolated cardiac myocytes using fluorescence and confocal microscopy. Our studies of GPCR modulation of cardiac physiology have focused primarily on the adenosine receptor system. We are currently examining signaling interactions in the cardiac myocyte between adenosine receptor subtypes (there are 4 known subtypes), as well as interactions between adenosine and opioid receptors. Adenosine and opioid receptor knockout mice will be used to investigate these interactions. Additional studies are planned to examine the role of oxidative stress and altered subcellular signaling in mediating the effects of aging and type 2 diabetes on cardiac function.