The effects of caffeine on the electrical properties of isolated, single rat ventricular cells.

Abstract

The effects of caffeine on ionic currents in isolated, single cells from rat ventricles were compared with the effects of adrenaline. In current-clamp experiments, caffeine (1.0 to 10.0 mM) increased both the height of the plateau and the duration of the action potential. Both caffeine and adrenaline increased the amplitude and duration of the slow responses. Voltage-clamp experiments reveal that the repolarization phase of the action potential in isolated cells is determined mainly by the slow inward current (Is), which has voltage-dependent kinetics similar to the IS in intact cardiac tissue. No evidence of a time-dependent outward current (4), or a hyperpolarization-induced inward current (4) or (If) was found, although a time-independent background current (41) was observed. Caffeine increased the amplitude of IS, but did not change its time course, its voltage dependency (of steady-state inactivation and activation), or its apparent reversal potential. Ikl is not affected by the caffeine. The results indicated that the effects of caffeine were nearly identical to those of adrenaline. The effects of caffeine on the electrical properties of single cells from rat ventricles derive chiefly from its action on I, channels.

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

“…Epinephrine enhances automaticity, lowers fibrillation thresholds [17,18,27,29,30] and increases extrasystoles [28,31]. The effects on the action potential vary, but epinephrine alters calcium handling and increases the likelihood of delayed after-depolarizations [32][33][34][35]. Nevertheless, at doses consistent with blood levels predicted in man [7], epinephrine did not show arrhythmic tendencies based upon the changes observed.…”

Caffeine‐induced decreases in the inward rectifier potassium and the inward calcium currents in rat ventricular myocytes

“…The change of the intracellular Ca2" concentration may affect the properties of various transmembrane ionic currents in the heart. Also, there are reports that caffeine may directly influence ionic currents (Goto et al, 1979;Eisner et al, 1979;Yatani et al, 1984;Habuchi et al, 1991). The effect of caffeine on the L-type Ca current is controversial.…”

“…The effect of caffeine on the L-type Ca current is controversial. Some studies suggest an increase of ICa (Goto et al, 1979;Yatani et al, 1984) probably due to the suppression of phosphodiesterase activity (Beavo et al, 1970). Other studies indicate an inhibitory action of caffeine on the ICa (Eisner et al, 1979;Hughes et al, 1990).…”

Two differential mechanisms of automaticity in diseased human atrial fibers.

“…The subsequent application of ryanodine (1 /IM) strongly suppressed these ouabaininduced fast-type AAPs and abolished the automaticity (bottom trace). Thus, most of the fast-type automaticity is presumably mediated by the cyclic release of Ca from the SR. Caffeine in high concentrations (>_ 5 mM) seems to interfere with a function of the SR (FABIATO and FABIATO, 1975) and to increase the slow inward Cat + current ('Ca) (Sc1m EIDER and SPERELAKIS, 1975;YATANI et al, 1984). As can be seen in Fig.…”

“…5A and 6B). Caffeine inhibits the activity of phosphodiesterase, increases intracellular cyclic AMP, and enhances the Ca current through the slow channel (SCHNEIDER and SPERELAKIS, 1975;YATANI et al, 1984). Ryanodine which has no direct effect on the Ica (SUTKO and KENYON,1983) failed to exert such effects (Figs.…”