Figure 3.

Voltage-dependent inhibition of I_Na by EPA in HEK293t cells expressing the wild type or three mutants of hH1_α Na⁺ channels. (A) Whole-cell currents were normalized by I_Na recorded with the conditioning voltage of −180 mV for their corresponding controls. The experimental protocol is shown in the Inset. Currents were elicited by 10-ms test pulses to 30 mV following a 10-s conditioning pulse varying from −180 mV to −50 mV with 10-mV increments. A 100-ms interval was inserted between the conditioning pulse and the test pulse. The membrane potential was held at −150 mV, and the pulse rate was 0.1 Hz. Except for the mutant F1760K, EPA at 5 μM did not show profound voltage-dependent suppression of I_Na for the wild type, Y1767K, and N406K with the protocol of a 100-ms recovery interval. (B) Voltage-dependent suppression of I_Na in the presence of 5 μM EPA is shown. The Inset is the voltage protocol with a recovery interval of 5 ms. EPA at 5 μM produced a profound voltage-dependent suppression of I_Na for the wild type, Y1767K, and F1760K, but the suppression for N406K is relatively less profound with the protocol of a 5-ms recovery interval. The data were fit with a Boltzmann equation.