Effects of External Acidosis on HERG Current Expressed in Xenopus Oocytes

T. Terai, T. Furukawa, Y. Katayama and M. Hiraoka. Effects of External Acidosis on HERG Current Expressed in Xenopus Oocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 11–21. 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 μ S by changing external pH (pHo) 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 pHo7.6 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 m to 10 m , a ratio of slope conductance at pHo6.0 to pHo7.6 was significantly smaller in 2 m (pHo6.0/pHo7.6=0.65±0.04) than in 10 m [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.