BK channels expressed in oocytes following injection of a 1:1 mixture of G375R mutant and WT cRNA activate at greatly left-shifted negative potentials compared with BK channels expressed following injection of only WT cRNA. (A) Whole-cell currents recorded from oocytes with the two-electrode voltage clamp for the indicated injections of cRNA. The whole cell currents were generated by holding the potential at −80 mV and then jumping to voltages ranging from −140 mV to +60 mV in 10 mV increments (1:1) or to +100 mV (WT and blank). (B) Plots of relative conductance versus the voltage of the steps following injection of a 1:1 mixture of mutant and WT cRNA (red diamonds); injection of WT cRNA alone (black circles); or injection of carrier only (purple triangles). The high conductance at negative potentials would act to drive the membrane potential to about −80 mV, the equilibrium potential of K⁺. Channel activation is left-shifted in the whole cell recordings in this figure compared to the essentially 0 Ca²⁺ macro patch recordings in Fig. 3 because the resting free Ca²⁺ in the oocytes of a few micromolar left shifts BK channel activation. The relative cord conductance was calculated from the plotted steady-state currents in Fig. S2 using the step potential minus the reversal potential for the voltage driving force. Mean ± SEM, n = 4 in each case.