The aim of this study was to investigate the effects of the potassium channel openers (PCOs) cromakalim and pinacidil on the ATP-dependent potassium current I(K)(ATP) in human atrial myocytes. Cells were isolated from the right atrial appendage obtained during cardiac surgery. Membrane currents were studied with the patch-clamp technique in the whole-cell recording mode at 36 degrees -37 degrees C. Under physiological conditions (4.3 mmol/l ATP in the pipette solution, ATPi) I(K)(ATP) did not contribute to basal electrical activity. When ATPi was omitted from the pipette solution I(K)(ATP) activated with a time lag of 4.92+/-0.92 min (n=6) and was completely inhibited by glibenclamide. Using 4.3 mmol/l ATPi I(K)(ATP) at +30 mV was increased by 2.04+/-0.51, 7.24+/-1.65 and 13.22+/-3.71 pA/pF (n=7) with 10, 30 and 100 micromol/l cromakalim, respectively, and by 3.24+/-0.98 (n=6), 4.07+/-0.48 (n=10) and 3.46+/-1.23 pA/pF (n=6) with 10, 30 and 100 micromol/l pinacidil, respectively. Control current density was 5.39+/-0.47 pA/pF (n=39). Using 1 mmol/l ATPi I(K)(ATP) showed a more pronounced activation (4.81+/-3.28, n=6; 9.78+/-2.60, n=7; and 15.1+/-4.18 pA/pF, n=6; with 10, 30 and 100 micromol/l pinacidil, respectively). I(K)(ATP) activated by both compounds could be effectively inhibited by glibenclamide. Repetitive exposure to pinacidil (30 micromol/l at 4.3 mmol/l ATPi) caused a potentiation of I(K)(ATP). Current density at +30 mV was increased by 87% during the first and by 401% during the second pinacidil application (n=5). The data presented in this paper provide new information about electrophysiological characteristics of human atrial I(K)(ATP) and its modulation by the PCOs cromakalim and pinacidil and suggest species-dependent differences.