This is a new application to acquire a Multisite Optical Mapping System to be shared among a scientifically strong and diverse group of PHS-supported investigations from 6 different departments at Washington University School of Medicine (Internal Medicine Cardiothoracic Surgery, Pathology, Cell Biology and Physiology, Molecular Biology and Pharmacology, Experimental Neurology and Neurological Surgery). Optical mapping technology does not exist at Washington University. Accordingly, acquisition of this instrumentation will have a major impact on the progress of current and future activities of the user group. The proposed applications of optical mapping are focused on 3 major areas of interest: 1) elucidation of molecular determinants of normal cardiac electrophysiology and delineation of mechanisms of arrhythmogenesis in mouse models in which the expression of genes encoding specific ion channels and other proteins is genetically manipulated; 2) identification of mechanisms of atrial and ventricular arrhythmias and characterization of novel therapies by integrated electrophysiological analysis in large animal models of human disease and in tissues obtained from heart disease patients; and 3) analysis of mechanisms underlying development and reactive plasticity of the central nervous system and mechanisms linking local neuronal activity and local cerebral blood flow. The requested instrumentation will be housed in a central core facility in the Center for Cardiovascular Research at Washington University School of Medicine. The composition of the user group is designed to facilitate scientific collaborations between basic scientists and clinical investigators and to encourage and enhance interactions between the cardiac electrophysiology and neurobiology communities at Washington University. This technical resource will also be crucial in our efforts to recruit new research faculty in molecular electrophysiology. Although there are no multisite optical mapping systems at Washington University, members of the user group have collaborated with laboratories recognized as world leaders in optical mapping application. They also have extensive experience in conventional (electrode-based) electrophysiological mapping in the use of related optical methods and computer systems applications in acquisition and analysis of complex data sets. The establishment of an optical mapping resource will enhance current and future research programs and scientific contributions by investigators at Washington University.
