Coordinated spread of electrical activity is an underlying mechanism which regulates gastrointestinal (GI) motility. Past analyses of electrical events have been limited to simplified, 1- dimensional """"""""cable"""""""" models. This investigation features the development and applications of a multi-dimensional, physiologic model of electrical behavior in smooth muscle syncytia based on the morphology of smooth muscle fibers and the electrical properties of excitable cells. By applying modern, """"""""finite- element"""""""" computational techniques, the model will be used to quantitatively describe electrophysiological responses in 3- dimensional tissues. Simulations will include: irregular tissue geometry, inhomogeneous electrical properties, extracellular impedance, complicated electrical waveforms and multi- dimensional spread of both active and passive electrical events. The model will also be used to describe the electrical """"""""filtering"""""""" of slow wave events and """"""""action potentials"""""""" by smooth muscle syncytia, and the integration of electrical activity in colonic circular muscle which lies between 2 pacemaker regions. Ultimately, our quantitative understanding of the electrical and mechanical behavior of GI muscles must be able to incorporate complex, multi-dimensional morphological and electrical interactions. As stated in the program announcement addressed by this application, mathematical modeling is a useful investigational strategy when closely coupled to biological experimentation. Descriptions of electromechanical activity in the GI tract will continue to be qualitative, unless a flexible model is developed which is firmly based on the electrical and morphological parameters of GI syncytia. The development of this model has the potential to reduce the overall numbers of animals used in experiments to address basic questions concerning electromechanical activity of the mammalian GI tract by providing: a basis for the analysis of data from experiments, a rigorous framework to make predictions and test hypotheses (even for experiments which are technically impossible), and a basis for preparing appropriate experimental protocols. This investigation is a basic step toward developing an integrated understanding of GI electrophysiology, motility and motility disorders.
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