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Enhancement and suppression of currents related to calcium-overload by different concentrations of methylxanthines
Abstract:
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.
Insights
Methylxanthines like caffeine affect cardiac ion currents differently based on concentration. These compounds influence oscillatory (Ios) and inward tail currents (Iex) in sheep Purkinje fibers, impacting calcium handling.
Area of Science:
- Pharmacology
- Cardiology
- Electrophysiology
Background:
- Methylxanthines, including theophylline, aminophylline, and caffeine, are widely used stimulants.
- Their effects on cardiac electrophysiology, particularly ion channel function, require detailed investigation.
Purpose of the Study:
- To investigate the concentration-dependent effects of theophylline, aminophylline, and caffeine on oscillatory (Ios) and inward tail currents (Iex) in sheep Purkinje fibers.
- To elucidate the role of cellular calcium load in mediating these effects.
Main Methods:
- Utilized a two-microelectrode voltage clamp technique.
- Applied varying concentrations of methylxanthines to sheep Purkinje fibers.
Main Results:
- Low methylxanthine concentrations shifted Ios induction to more negative potentials, increased Ios magnitude, and shortened its time to peak.
- High concentrations of aminophylline and caffeine abolished Ios, while theophylline reduced it.
- Methylxanthine concentrations increased the magnitude of Iex.
- Effects were exaggerated with larger depolarizing clamp steps, indicating calcium load dependence.
Conclusions:
- Theophylline exhibits qualitatively similar but quantitatively smaller effects on Ios and Iex compared to caffeine.
- Methylxanthines differentially affect Ios and Iex based on concentration, suggesting altered cellular calcium handling.