1. A large body of evidence indicates that elevated homocysteine (Hcy) levels portend an increased risk for atrial fibrillation. However, little is known about the electrophysiological effects of Hcy on atrial myocytes. The present study was conducted to investigate the direct effects of Hcy on ion channels in human atria. 2. Whole-cell patch-clamp techniques were used to record potassium currents in human atrial cells. 3. In human atrial myocytes, transient outward potassium currents were significantly decreased by 24.8 +/- 5.9 and 38.4 +/- 10.4% in the presence of 50 and 500 micromol/L Hcy, respectively. The ultrarapid delayed rectifier potassium currents were decreased by approximately 30% when exposed to 500 micromol/L Hcy. The inward rectifier potassium currents were increased by approximately 40% in the presence of 500 micromol/L Hcy. 4. The results of the present study indicate that Hcy, an important risk factor for atrial fibrillation, could cause electrophysiological disturbances of potassium currents in human atrial myocytes.