Figure 3.

Mibefradil inhibits different types of K⁺ currents of fusion-competent myoblasts. All experiments were done with fusion-competent myoblasts exposed to differentiation medium for 3 days. (A) A myoblast (membrane capacitance 18 pF) was held steadily at −80 mV and stepped for 500 ms to a series of voltages between −80 and +40 mV. The outward current obtained at the end of the step was plotted as a function of the voltage during a step in the absence and in the presence of 3 μM mibefradil. Leak current was obtained by linear extrapolation from the current-voltage relationship between −80 and −40 mV and subtracted. This cell had no I_h-eag, so that the outward current represents exclusively I_K(DR). Currents recorded from the same cell (during a step to +40 mV) without and with 3 μM mibefradil are shown. (B) Another fusion-competent myoblast (membrane capacitance 17 pF) was held steadily at +40 mV for 3 min, and stepped for 500 ms to a series of voltages between −80  and +40 mV. Symbols represent the amplitude of I_h-eag recorded in the absence and in the presence of 3 μM mibefradil. Leak current was obtained as in (A) and subtracted. Steady-state currents at +40 mV in the absence and in the presence of 3 μM mibefradil are shown (same cell). The dotted line indicates the leak at +40 mV. (C) A fusion-competent myoblast (membrane capacitance 26 pF) expressing I_K(IR) was held steadily at −60 mV and stepped to a series of voltages between −120 and −40 mV for 500 ms. Leak subtracted I_K(IR) currents measured in the absence and in the presence of 10 μM mibefradil were plotted against the voltage during the step. Leak current was obtained by adding 500 μM Ba²⁺ to the bath solution. Inward K⁺ currents recorded from the same cell at −120 mV in the absence and in the presence of 10 μM mibefradil are shown. (D) I_K(DR), I_h-eag, and I_K(IR) normalized to their respective control values are plotted as a function of mibefradil concentration. The three data sets were fitted with a Hill equation.