Activation rates of double-deletion mutants were significantly slower than those of WT channels and those of N- and C-terminal single-deletion mutants. A, normalized tail currents were plotted versus activation pulse duration for WT HERG, HERGNΔ12CΔ236, HERGNΔ12CΔ278, HERGNΔ354CΔ236 and HERGNΔ354CΔ278 at +40 mV (symbols indicated in figure). Activation time constants were fitted with a single-exponential function (see Fig. 4 for details; n = 17, P = 0.408). B, activation time constants at +40 mV for WT HERG, HERGNΔ12 and HERGNΔ354 are shown (n = 17, P = 0.044). Time constants were calculated from exponential fits (symbols indicated in figure). C, activation time constants of WT HERG, HERGNΔ12CΔ236, HERGNΔ12CΔ278, HERGNΔ354CΔ236, HERGNΔ354CΔ236, HERGNΔ12 and HERGNΔ354 are summarized in this bar graph (n = 17). D, slope values of activation curves at +40 mV for the constructs above (n = 17).