Fig 1. Effects of mexiletine and lidocaine on voltage-dependent activation of Na_v1.5 and Na_v1.7 channels.

A, B, Representative activation traces were recorded in HEK293 cells stably expressing either Na_v1.5 (A, left panel) or Na_v1.7 (B, left panel) channels. In the presence of 0.3 mM mexiletine (middle panel) or lidocaine (right panel), the peak currents of both channels evoked by 50 ms pulses to -20 mV were inhibited. The protocol of voltage-dependent activation is shown in A inset. C, Normalized conductance versus voltage was plotted for Na_v1.5 (left panel) and Na_v1.7 (right panel) channels. Curves were fitted by Boltzmann function: G/Gmax = 1-1/ (1 + exp ((V-V_1/2)/k)). The V_1/2 and slope factor (k) of Na_v1.5 and Na_v1.7 channels are listed in Table 1. Mexiletine and lidocaine caused no significant shift of V_1/2 and slope factor for both Na_v1.5 and Na_v1.7 channels. D, Effects of mexiletine and lidocaine on inactivation kinetics. The inactivation decay time constants were estimated with one exponential fit from the decay of current elicited by a 50 ms pulse to indicated voltages. Mexiletine or lidocaine slightly but no significantly accelerated the decay phase of Na_v1.5 at -40 mV and -35 mV (left panel), whereas slightly accelerated decay of Na_v1.7 inactivation was only found at -40 mV (right panel).