Enhancement and suppression of currents related to calcium-overload by different concentrations of methylxanthines.

The actions of different concentrations of theophylline, aminophylline and caffeine on the oscillatory current (Ios) and on the inward tail current (Iex) were studied in sheep Purkinje fibers by means of a two microelectrode voltage clamp technique. The following results were obtained. At a low concentration (1 mM), the methylxanthines shifted to a more negative value the depolarization needed for the subsequent induction of Ios, increased the magnitude and shortened the time to peak of Ios. At a high concentration (8 mM), aminophylline and caffeine abolished Ios whereas theophylline only reduced it. However, at 16 mM, also theophylline markedly reduced Ios. In contrast, the magnitude of Iex increased with increasing concentrations of methylxanthines. Intermediate concentrations of the methylxanthines had intermediate effects. The actions of methylxanthines on Ios and Iex were exaggerated following larger depolarizing clamp steps, suggesting a dependence on cellular calcium load. It is concluded that theophylline has actions of Ios and Iex that are qualitatively similar to those of caffeine but are quantitatively smaller. In addition, the methylxanthines affect Ios and Iex differently depending on the concentration and this concentration-dependence appears to reflect a change in the way the cell handles calcium load.