Figure 1.

Rundown of hERG and reversal by PIP₂ application. Data from a giant patch of a representative COS-7 cell transfected with hERG and studied in the inside-out configuration. (A) hERG current in response to an activation protocol (left), an inactivation protocol (middle), and an envelope protocol (right). Tail currents are proportional to the activation of hERG in the first protocol. Peak currents divided by the electromotive force are proportional to the extent of inactivation in the second protocol. Peak currents represent the time course of channel activation in the envelope protocol. Shown are the control current after excision (t = 60 s), the current after rundown (t = 1076 s), and the current after addition of PIP₂ (t = 1757 s, 5 μmol/L PIP₂ is added at t = 1200 s). (B) Activation curve (left), inactivation curve (middle), and time course of the peak inward current amplitude (right) at −10 mV, obtained from the recordings shown in A. Activation and inactivation curves are fitted by Boltzmann equations. The measurement points (symbols) and fits (lines) are indicated for control (triangles, solid line), after rundown (circles, dashed line); and after PIP₂ addition (squares, dotted line). (C) Kinetics of hERG biophysical parameters during rundown and after 5 μmol/L PIP₂ addition. These parameters are measured from the activation protocol repeated every 16 s. Solid symbols indicate maximal current, −100 mV deactivation, and recovery-from-inactivation time constants; open symbols indicate half-activation potential and −55 mV activation time constant.