Cardiac inward rectifier potassium current IK1 is inhibited by acetaldehyde at clinically relevant concentrations: a role in arrhythmogenesis related to alcohol consumption?
|Název česky||Srdeční inward rectifier proud IK1 je inhibován acetaldehydem v klinicky relevantních koncentracích: role v arytmogenezi vázané na konzumaci alkoholu?|
|Fakulta / Pracoviště MU|
|Popis||Purpose: Alcohol intoxication may induce electrocardiographic changes and arrhythmias. Modifications of cardiac inward rectifier potassium currents including IK1 are known to play an important role in the pathogenesis of various types of arrhythmias including those observed under alcohol intoxication. We have recently published a study describing a significant effect of ethanol at clinically relevant concentrations on the ventricular IK1. In the current study, we aimed to analyse changes of the ventricular IK1 in the presence of acetaldehyde, the primary metabolite of ethanol. Methods: Experiments were performed on enzymatically isolated rat ventricular myocytes by the whole cell patch clamp technique at 23 ± 1 °C. IK1 was analysed as the current sensitive to 100 µM Ba2+. Solutions were applied into the near surrounding of the measured cell with a rapid perfusion system. Results: Acetaldehyde (0.3 – 300 µM) induced a reversible inhibition of IK1 with the concentration causing 50% inhibition (IC50) of 53.7 ± 7.7 µM at -100 mV. A significant inhibition was documented even at clinically relevant concentrations; namely 3 µM acetaldehyde reduced IK1 by 13.1 ± 3.0% of. Both development and wash-out of the acetaldehyde effect on IK1 showed a single exponential time course with average time constants of 24.5 ± 3.5 s and 41.5 ± 3.6 s at 3 µM, respectively. The inhibition was voltage-dependent between -120 and -80 mV; at -80 mV and more positive voltages, the inhibition was by about 10% lower than at -100 mV. Conclusions: We conclude that the observed changes of IK1 under clinically relevant concentrations of acetaldehyde might contribute to the alcohol-induced alterations of the cardiac electrophysiology, namely in people with a genetic defect of aldehyde dehydrogenase and, thus, higher plasma levels of acetaldehyde who are often native to Asia.|