Linear dependence of the GOF and DOF effects of the G375 mutation on the number of mutant subunits in the BK channel tetramer. In the top row, cartoons depicting the six potential subunit arrangements for BK channel tetramers from WT (grey) and mutant (blue) subunits, with the corresponding percentage populations of the assembled channels based on the theoretically predicted and experimentally suggested values given below. The next two rows depict, respectively, the expected voltage-dependence of Po and the idealized single-channel currents recorded at +100 mV for each of the six assembled channels. The Po-versus-voltage plots for homomeric WT channels are black and mutant channels of a given stoichiometry are in red. The plots in dashed black lines correspond to the Po-versus-voltage plots for homomeric WT channels shown to illustrate the shift in V1/2 due to the incorporation of mutant subunits. The horizontal red arrows illustrate the shift of approximately −60 mV in V1/2 each time a mutant subunit is exchanged for a WT subunit and vertical red arrows illustrate the decrease of ∼10% in the single-channel conductance each time a WT subunit is exchanged for a mutant subunit.