Development of resting inactivation of INa,α in HEK293t cells expressing hH1α directly from the resting, activatable state. (A) The pulse protocol shows a depolarizing pulse from a holding potential of −150 mV to −65 mV. With progressively longer values of Δt at −65 mV an increasing proportion of hH1α transited directly to their inactivated state. This is followed by a 10-ms test pulse to −30 mV. Current traces of INa,α in the absence (B) and presence (C) of 5 μM EPA (n = 6). The membrane potential was held at −150 mV and cycling frequency was 0.2 Hz. (D) The effects of prolonging the time at −65 mV (during which increasing numbers of hH1α channels slipped directly from their resting state into their inactivated state) on the normalized currents in the presence and absence of EPA are shown. In the presence of EPA the time constant for the development of inactivation was significantly decreased [control 26.2 ± 0.78 ms, n = 6 and EPA (5 μM) 3.67 ± 0.22 ms, n = 6, P < 0.01)].