Electrophysiological properties of hNav1.5 and mutant T1620K channels.
(A) Steady-state activation as function of voltage. (B) Time constants of inactivation as function of voltage. The Na+ current decay was fitted with a monoexponential function. (C) Steady-state inactivation as function of voltage. (D) Recovery from inactivation. (E) Illustration of the window current in hNav1.5 (light gray) and T1620K (dark gray). Due to the hyperpolarizing shift of steady-state activation (A) and the increased slope of the steady-state inactivation curve (C) both the amplitude and the voltage range of the window current is increased. Gain-of-function features, most likely resulting in prolonged ventricular action potentials and thus in LQT3, are the slower current decay at potentials positive to −40 mV (B), the faster recovery from inactivation (D), and the larger window current (E) , . Loss-of-function features, most likely resulting in conduction slowing and thus in CCD, are the faster current decay at potentials negative to −40 mV (B), and the reduced steady-state availability at the resting membrane potential (C) , . Individual curves illustrating steady-state activation (A), steady-state inactivation (C), and recovery from inactivation (D) were drawn using three representative measurements. Bars indicate S.E.M. For total number of measurements and statistical data evaluation see Table 2. The corresponding peak current densities are shown in Table 3.