Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner

Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current I K1 , known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10–100 µM) on I K1 did not significantly differ in healthy porcine and failing human ventricular myocytes. I K1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 µM aminophylline, respectively, at −110 mV; an analogical effect was observed at −50 mV. To separate the impact of I K1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 µM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific I K1 inhibitor Ba 2 + (10 µM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human I K1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored. • The bronchodilator aminophylline may induce arrhythmias. • The mechanism of the proarrhythmic action of aminophylline is not well understood. • Aminophylline interacts with I K1 channels causing their inhibition on average. • The effect was similar in healthy porcine and failing human cardiomyocytes. • The observed effect of aminophylline might be involved in its proarrhythmic action.