EFFECT OF ETHANOL AND ACETALDEHYDE AT CLINICALLY RELEVANT CONCENTRATIONS ON ATRIAL INWARD RECTIFIER POTASSIUM CURRENT IK1 SEPARATE AND COMBINED EFFECT

Atrial fibrillation is the most common arrhythmia at alcohol consumption. Its pathogenesis is complex, at least partly related to changes of cardiac inward rectifier potassium currents including I-K1. Both ethanol and acetaldehyde have been demonstrated to considerably modify I-K1 in rat ventricular myocytes. However, analogical data on the atrial I-K1 are lacking. The present study aimed to analyse I-K1 changes induced by ethanol and acetyldehyde in atrial myocytes. The experiments were performed by the whole cell patch-clamp technique at 23 +/- 1 degrees C on enzymatically isolated rat and guinea-pig atrial myocytes as well as on expressed human Kir2.3 channels. Ethanol (8 - 80 mM) caused a dual effect on the atrial I-k1 showing the steady-state activation in some cells but inhibition in others in agreement with the ventricular data; on average, the activation was observed (at 20 mM by 4.3 and 4.5% in rat and guinea-pig atrial myocytes, respectively). The effect slightly increased with depolarization above -60 mV. In contrast, the current through human Kir2.3 channels (prevailing atrial I-K1 subunit) was inhibited in all measured cells. Unlike ethanol, acetaldehyde (3 mu M) markedly inhibited the rat atrial I-K1 (by 15.1%) in a voltage-independent manner, comparably to the rat ventricular I-K1. The concurrent application of ethanol (20 mM) and acetaldehyde (3 mu M) resulted in the steady-state I-K1 activation by 2.1% on average. We conclude that ethanol and even more acetaldehyde affected I-K1 at clinically relevant concentrations if applied separately. Their combined effect did not significantly differ from the effect of ethanol alone.