FIGURE 2.

Three-dimensional surfaces of n_H (V = V_1/2) and V_1/2 as a function of both K_A and K_B using identical scales. The graph for n_H was plotted based on Eq. 9 and that of V_1/2 according to the equation derived using the condition of half-activation (P_O = 1/2). Unitary gating charge of 3 was assumed for Z. The main diagonal trajectory where K_A = K_B separates positive ((K_B/K_A) > 1) and negative ((K_B/K_A) < 1) coupling domains to the right and left of this diagonal, respectively. Three extreme scenarios may be envisaged: 1), along the main diagonal trajectory; increasing K_A and K_B upon mutations, for example, would shift the midpoint activation voltage to the left to more negative voltages; however, n_H would not change. 2), The trajectory in bold corresponds to a case in which increasing K_B only would result in a shift of the midpoint activation voltage to the left in parallel with steeper n_H slopes. 3), Opposite dependence is observed between n_H and V_1/2 for a case in which only K_A is changed upon mutations.