The effect of lithium ions on cardiac cells was investigated by recording the changes in transmembrane potential and by following the movement of Li, Na, and K across the cell membrane. Isolated preparations of calf Purkinje fibers and cat ventricular muscles were used. Potentials were measured by intracellular microelectrodes; ion transport was estimated by flame photometric analysis and by using the radioactive isotopes of Na and K. It was shown (a) that Li ions can replace Na ions in the mechanism generating the cardiac action potential but that they also cause a marked depolarization and pronounced changes in action potential configuration; (b) that the resting permeability to Li ions is high and that these ions accumulate in the cell interior as if they were not actively pumped outwards. In Li-Tyrode [K]i decreases markedly while the K permeability seems to be increased. In a kinetic study of net K and Na fluxes, the outward movement of each ion was found to be proportional to the second power of its intracellular concentration. The effect on the transmembrane potential is explained in terms of changes in ion movement and intracellular ion concentration.

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