Maintenance of coupling strength between cardiac myocytes is essential for normal electrical activity. That strength depends primarily on intracellular gap junction coupling and on interstitial coupling in the cleft space. Each flow path is well recognized and there is considerable evidence to suggest micro-impedance changes are important for arrhythmia initiation and maintenance. However, no procedure or standard instrument for measuring intracellular and interstitial conductivities (the inverse of impedances) has been available, so information on their magnitudes is limited. This proposal will evaluate novel theoretical and experimental approaches that, if successful, will allow intracellular, interstitial and membrane micro-impedance measurements to become a straightforward component of cardiac electrophysiologic study because no intracellular access is required. A straightforward measurement procedure would have an enormous impact on theoretical analyses, as modeling studies presently rely upon incomplete impedance data. Further development of our initial research in this Exploratory Bioengineering Research Grant (EBRG) will allow us to establish sufficient expertise to design an RO1 scale Bioengineering Research Grant (BRG) at the project's end. The project has two aims: (1) to refine the integrated theoretical and experimental approach and minimize errors in micro-impedance measurements and (2) to develop microfabricated sensor arrays for micro-impedance measurements.
