A System for 3D Optical Action Potential Measurements

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DESCRIPTION (provided by applicant): A significant limitation in the investigation of electrophysiological phenomena has been the inability to measure transmembrane action potentials in three dimensions in excitable tissue. 3D measurements have been made using traditional voltametric electrodes, but information about electrical repolarization of cell membranes is lost or compromised. The shape of the action potential can be appreciated through the use of optical methods and voltage sensitive dyes, but in general this technique is limited to two dimensions. In the R21 phase of this application, it is proposed to demonstrate the feasibility of using a prototype optical fiber-based device (optrode) for making reliable, repeatable and effective measurements of action potentials in 3D cardiac tissue. Issues to be addressed in the feasibility phase include signal to noise ratio, size and shape of tissue volume interrogated, fidelity of recordings, achievable spatial resolution, and tissue disruption. A small, multioptrode system that is easily expandable to a full 256 fiber configuration will be developed, demonstrating the feasibility of fabrication and use. During the R33 phase of the grant, a complete system will be assembled to allow data acquisition, analysis, and display during physiological investigations. The software development will use open, industry standard programming environments to allow easy dissemination to the scientific community. The successful completion of this work has broad ramifications. By using a variety of dyes with the same basic system, it will be possible to use optical methods to measure pH, calcium transients, and other variables in 3D structures with minimal effect on the studied tissue. These new capabilities will provide new avenues of research for cardiac electrophysiologists and others studying 3D phenomena in electrically excitable tissue.