Figure 4.

I_hERG inactivation and KB-R7943. (A) Protocol used to investigate I_hERG‘availability’. From −80 mV, the membrane potential was stepped to +40 mV for 500 ms; this was then followed by 2 ms repolarization steps to potentials ranging from −140 to +50 mV. Membrane potential was then stepped back to +40 mV for 100 ms (inset shows portion of protocol encompassing the transition to and from repolarizing steps). The amplitude of current transients elicited by the second step to +40 mV was used to assess I_hERG availability. (B) Plots against voltage of normalized current transient amplitude in control and in 100 nM KB-R7943 (n= 8 cells); a Boltzmann equation was used to derive the V_0.5 and k values shown in the Results text. (C) Three-step protocol used to assess the effect of promoting I_hERG inactivation on the action of KB-R7943. Protocol is shown as lower trace; upper traces show representative currents in control, in the presence of 100 nM KB-R7943 and following exposure to 5 µM E-4031. (D) Mean level of fractional block at three time points during the protocol (n= 7). The three time points are given with reference to the start of the acquisition period (200 ms before the initial depolarization to 0 mV).