Figure 5. Comparison of recovery from inactivation of hERG and the S1–S6 chimaera.

(a) The three stage voltage protocol used to measure recovery from inactivation. Voltage was first stepped from −80 mV to + 35 mV to fully inactivate the channels, then stepped from −145 to +35 mV, in 10 mV increments, followed by a third +35 mV step, and then a final −145 mV step to relieve inactivation. (b) Representative current traces for hERG and the chimaera using the protocol shown in (a). The scaled-up traces show currents during the third +35 mV step; they represent the currents recovered from inactivation during the preceding voltage steps. (c) Voltage-dependence of the recovery from steady-state inactivation. The normalised peak recovered currents were plotted against voltage and fitted with a Boltzmann function. There was a significant (p < 0.05,) rightward shift in the V_1/2 value of ≈40 mV for the S1–S6 chimaera (−17.09 ± 2.37, n = 12) compared to hERG (−60.47 ± 6.20 mV). (d) Voltage dependence of the time to reach peak current (I_Max); the S1–S6 chimaera takes significantly (p < 0.05) longer time compared with hERG to reach peak current over the voltage range examined.