Effects of external acidosis on HERG current expressed in Xenopus oocytes.
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).
Terai
T
T
Department of 1st Internal Medicine, School of Medicine, Tokyo, 113-8510, Japan.
Furukawa
T
T
Katayama
Y
Y
Hiraoka
M
M
D000818:Animals; D027682:Cation Transport Proteins; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009865:Oocytes; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D014982:Xenopus laevis
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated