Induction of the oscillatory current by low concentrations of caffeine in sheep cardiac Purkinje fibres

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Abstract
The actions of low concentrations of caffeine (0.5–2 mmol/1) on the transient inward oscillatory current (Ios) and the inward tail current (Iex) were studied in sheep cardiac Purkinje fibres by means of a two microelectrode voltage clamp method. The following results were obtained. Caffeine: 1. induced an Ios when this current was not already present; 2. increased the amplitude (within limits) and consistently decreased the time to peak of an already present Ios; 3. increased Iex upon which Ios may be superimposed; 4. shifted the depolarizing threshold for the appearance of Ios to more negative and the repolarizing threshold to less negative values; 5. increased the effects of strophanthidin of Ios and Iex; 6. exaggerated the effects of high [Ca]o which by itself mimicked some of the actions of caffeine; 7. had a small effect of Ios and Iex in low [Ca]o; 8. reversed the effect of norepinephrine on Iex; 9. enhanced the effects of trains of clamps and of longer clamp steps on Ios and Iex. It is concluded that low concentrations of caffeine facilitate the manifestations of calcium overload thereby inducing or exaggerating the oscillatory and tail currents and that these effects are modulated by the cellular calcium load but are not mediated through adrenergic mechanisms.