? ? This application requests funding to support the 2008 Grover Conference on the Pulmonary Circulation, entitled """"""""Membrane Receptors, Channels and Transporters in the Pulmonary Circulation: Role in the Development of Pulmonary Vascular Disease."""""""" ? ? Receptors, channels and transporters play critical roles in signal transduction, and are key elements in the development and progression of pulmonary vascular disease (PVD) progression. They represent the frontline mechanisms regulating fibroblast, smooth muscle and endothelial cell homeostasis, and for responding to the extracellular environment and intercellular mediators. Perturbations in membrane receptor and ion channel function and expression cause profound alterations in cellular function and significantly contribute to pathogenesis and progression of PVD. ? ? Over the past decade, there have been significant advances in our understanding of the expression and function of novel membrane receptors, channels and transporters in the pulmonary circulation. Several new molecular classes of ion channels (e.g., TRP and two-pore domain K+ channels) have been shown to play key roles in pulmonary vascular function. Enhanced molecular techniques, gene knockout models, and the human genome project have provided further insight into the molecular identity and role of ion K+ and Cl channels, aquaporins and intracellular Ca2+ channels in pulmonary vascular function and disease. The association between disease development and bone morphogenetic protein receptor II (BMPRII) mutations represents a major advance in the field. There are significant interactions between BMPR, serotonin receptors and transporters, and ion channels; such interrelationships will likely define a significant proportion of the altered contractility and remodeling in pulmonary vascular disease. We see a need for a forum where these mechanisms and pathways can be discussed to reveal potential converging therapeutic opportunities. ? ? The 2008 Grover Conference provides a forum for experts in the fields of pulmonary vascular pathobiology and clinical management of pulmonary vascular disease to rigorously address 1) recent advances in our knowledge of membrane receptors, channels and transporters and their role in regulation of pulmonary vascular function; 2) the interrelationships that contribute to the pathogenesis of pulmonary vascular disease, and 3) the therapeutic opportunities that may exist. (End of Abstract) ? ? ?
