Caffeine affects four different ionic currents in the bull‐frog sympathetic neurone.

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Abstract
1. Ionic mechanisms related to the caffeine‐induced current (Icaffeine) were examined in the single isolated sympathetic neurones of the bull‐frog. We used the ‘concentration‐jump’ technique in combination with intracellular perfusion and a rapid external solution change, under single‐electrode voltage‐clamp conditions. 2. Icaffeine was pharmacologically separated into a tetraethylammonium (TEA)‐sensitive transient outward current (ITO), a picrotoxin (PTX)‐sensitive transient inward current (ITI) and a TEA‐ and PTX‐insensitive sustained inward current (ISI). At low concentrations of caffeine, a sustained outward current (ISO) was observed instead of ISI. 3. All components of Icaffeine were abolished by intracellular perfusion of 30 mM‐EGTA. Pre‐treatment with A23187 or ryanodine or the simultaneous application of procaine either reduced or abolished all the components of Icaffeine in a dose‐dependent manner. The concentration causing 50% inhibition (IC50) was 10(‐8) M for A23187 and 2 mM for procaine. 4. The peak response of ITO increased abruptly at caffeine concentrations between 3 and 6 mM followed by saturation above 30 mM. A notch was observed on the rising phase of ITO. 5. The reversal potential (Ecaffeine) of ITO shifted 58 mV for a tenfold change of the extracellular K+ concentration. External application of TEA blocked ITO with an IC50 of 1 mM. ITO was relatively insensitive to apamin, 4‐aminopyridine and muscarine. 6. In external solution containing 2 mM‐Ca2+, ITO induced by 10 mM‐caffeine recovered completely within 3 min from a previous exposure to caffeine. In the absence of extracellular Ca2+, there was little such recovery. A 5 min treatment in a Ca2+‐free solution reduced ITO induced by the first application of caffeine by 5%. With a continuous application of 3 mM‐caffeine, the amplitude of ITO induced by 10 mM‐caffeine reduced in 1 min, and showed a partial recovery in 3 min. The amplitude of ITO increased by increasing the concentration of intracellular Cl‐. 7. ITI was activated around the peak of ITO and was rapidly inactivated. ITI was evoked at caffeine concentrations of about 6‐10 mM. When the intracellular Cl‐ concentration was changed, the amplitude of ITI behaved like a Cl‐ electrode. The Ecaffeine of ITI was close to the Cl‐ equilibrium potential (ECl). 8. ISI was a ‘plateau’ response and persisted for over 3 min. ISI was due to a decrease in K+ conductance. In the presence of muscarine (3 x 10(‐5) M), ISI was occluded.(ABSTRACT TRUNCATED AT 400 WORDS)