PROJECT SUMMARY/ABSTRACT Failure of the right ventricle (RV) is a main component of the morbidity and mortality of pulmonary hypertension (PH). There exists no specific treatment for RV dysfunction and failure and the only cure for many patients (especially in the case of pulmonary arterial hypertension) remains transplantation. This is partially due to the critical lack of understanding of RV biology; therapeutic strategies that are beneficial for LV failure have worse outcomes when applied to those with RV failure. What has been observed in RV dysfunction in human subjects and animal models is exaggerated fibrosis and divergent contractile and hypertrophic responses to several drugs when compared to LV dysfunction. Thus, the RV may contain distinct pathobiology compared to the LV that has high significance for treatment of PH. Cardiac myocytes may have distinct cell signaling properties in the RV, though there is a lot unknown about these differences. Previous work has shown that RV cardiac myocytes, compared to those from the LV, have increased K+ current, shorter action potential duration, reduced sarcomere shortening, and reduced peak intracellular Ca2+ when compared to LV cardiac myocytes. These differences demonstrate that RV cardiac myocytes may have molecular differences at a functional level. This diversity supplement will determine how contractility, calcium handling, and size of the cardiac myocyte change during RV remodeling in PH, and determine and test novel drug targets that alter RV contractility. These data may uncover novel understanding of RV cardiac myocyte biology and lead to further therapeutic strategies for right heart failure. This supplement will address this concern with two Specific Aims: (1) Determine the mechanism of cardiac myocyte adaptation to RV pressure overload. and (2) Interrogate GPCR targets in the RV as potential therapeutic targets.