The purpose of this study is to measure intracellular ionic activities in heart muscle, to determine how these activities are regulated and the effects of changing those activities on the electrical activity of the cells. At the present time the emphasis is on intracellular K ion and Cl minus. With Cl minus microelectrodes it has been established that Cl minus is not in electrochemical equilibrium in cat papillary muscle, but is transported into the cells. A suitable Na ion substitute is being sought so that extracellular Na ion can be changed while maintaining Cl minus constant. In this way the Na ion electrochemical gradient can be altered to test the hypothesis that the Na ion electrochemical gradient is the source of energy for the co-transport of Cl minus, with Na ion, into the cells. It has been demonstrated that in canine cardiac Purkinje cells, the depolarization resulting from ouabain intoxication is not due to a decrease in intracellular K ion causing an increase in the K ion equilibrium potential. Substitution experiments have shown that during ouabain intoxication the membrane potential becomes less dependent on K ion and more dependent on Na ion, when compared to control. Cl minus does not have any effect in either situation. Work is continuing to try and perfect double-barrel liquid ion exchanger microelectrodes with a total tip diameter of less than 0.5 microns.