We investigated effects of external acidosis on HERG current expressed in Xenopus oocytes. HERG current was rapidly and reversibly suppressed by external acidosis in a voltage-independent manner. The slope conductance was decreased from 143 +/- 11 to 93.4 +/- 6.8 microS by changing external pH (pH(o)) from 7.6 to 6.0 (P<0.05). Steady-state activation was shifted by about 20 mV in a depolarized direction with a change from pH(o) 7.6 to 6.0, while steady-state inactivation was not significantly changed. Activation time constants were increased, deactivation and recovery time constants were decreased, while those of inactivation showed no significant change. When external K(+) concentration ([K(+)](o)) was increased from 2 mM to 10 mM, a ratio of slope conductance at pH(o) 6.0 to pH(o) 7.6 was significantly smaller in 2 mM (pH(o) 6.0/pH(o) 7.6 = 0.65 +/- 0.04) than in 10 mM[K(+)](o) (0.83 +/- 0.06, P<0.05). The changes in activation, deactivation and recovery from inactivation were not affected by change in [K(+)](o). The results indicated that external acidosis suppressed HERG current mainly by shifting the voltage-dependence of the activation and deactivation kinetics, and partly by decreasing slope conductance. Moreover, the reduction of HERG current could be partly antagonized with increasing [K(+)](o).