Acetaldehyde at Clinically Relevant Concentrations Inhibits Inward Rectifier Potassium Current I-K1 in Rat Ventricular Myocytes

摘要

Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I-K1 in arrhythmogenesis, this study was aimed at the effect of acetaldehyde, the primary metabolite of ethanol, on IK1 in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I-K1 with IC50 = 53.7 +/- 7.7 mu M at -110 mV; a significant inhibition was documented even at clinically-relevant concentrations ( at 3 mu M by 13.1 +/- 3.0 %). The inhibition was voltage-independent at physiological voltages above -90 mV. The I-K1 changes under acetaldehyde may contribute to alcohol-induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of aldehyde dehydrogenase where the acetaldehyde level may be elevated.