title: Effects of external acidosis on HERG current expressed in Xenopus oocytes.
abstract: 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).
authors.affiliation: Department of 1st Internal Medicine, School of Medicine, Tokyo, 113-8510, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Terai
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: 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
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated