The objective of the proposed research is to further elucidate the ionic mechanisms underlying the myocardial action potential and excitation-contraction coupling. The principal experimental approach will be the single sucrose gap, micro-electrode voltage-clamp, and the experiments will be closely coupled with a numerical model of the events and preparation under study. The modelling is necessitated by the complexity of the experimental preparation being used. The fact that the preparations (trabeculae carnae and papillary muscles with an in vivo length of 3-5 mm and diameter less than .7 mm) are made up of a complex geometry of many individual cells imposes definite restrictions on the application of voltage clamp techniques. As a result, the experiments will include further studies on the passive character of the preparation, and these data will be combined with the dynamic, clamp, measurements in the model in order to continually assess the reliability of the ionic current measurements. Presently available theoretical analyses of the passive characteristics of these preparations do not predict the degree of clamp reliability that can be observed experimentally. It is hoped that multiple electrode studies, one electrode serving the clamp, and a second mapping potential variations in the preparations will allow resolution of this dichotomy. Experimental measures to date have yielded preliminary data on dynamic inward currents of sodium and calcium ions, and have shown the presence of two components of outward current, predominantly potassium. Of major interest is the behaviour of the calcium influx, and its relation to contraction. While this influx does not go directly to the contractile machinery, it does influence contraction on subsequent beats. By imposing electrical and pharmacological changes on these currents, and correlating these changes with contractile changes, it is possible to obtain more detailed information about the movement and sequestration of calcium within the cell.