Effects of caffeine on potassium currents in isolated rat ventricular myocytes

Rapid exposure of cardiac muscle to high concentrations of caffeine releases Ca2+ from the sarcoplasmic reticulum (SR). This Ca2+ is then extruded from the cell by the Na+/Ca2+ exchanger. Measurement of the current carried by the exchanger (I-Na/Ca) can therefore be used to estimate of the Ca2+ content of the SR. Previous studies have shown that caffeine, however, can also inhibit K+ currents. We therefore investigated whether the inhibitory effects of caffeine on these currents could contaminate measurements of I-Na/Ca. Caffeine caused partial inhibition of the inward rectifier K+ current (I-K1): the outward current at -40 mV was 1.15+/-0.24 pA/pF in control and decreased to 0.34+/-0.15 pA/pF in the presence of 10 mmol/l caffeine (P<0.05, n=15). This was similar to the effect of caffeine on the holding current observed at -40 mV in the absence of K+ channel block and could therefore account for the contaminating effects of caffeine observed during measurements of I-Na/Ca. Moreover, caffeine also partially inhibited the transient outward (I-to) and the delayed rectifier (I-K) K+ currents.