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Figure 5 Gating Properties for M1875T Channels
Detailed parameters are given in Table 2. (A) Voltage dependence of relative sodium (Na+) conductance activation and steady-state inactivation were determined by means of the voltage protocols, as shown in the inset. Curves were fit with the Boltzmann equation, I/Imax = (1 + exp[V–V1/2]/k)–1 to determine the membrane potential for half-maximal inactivation or activation (V1/2) and the slope factor k. Note that M1875T channels showed a pronounced depolarized shift (+16.4 mV) in the V1/2 of steady-state inactivation compared with wild-type (WT). (B) Time course of recovery from inactivation was elicited with a double pulse protocol. Data were fit with a 2 exponential equation: I/Imax = Af x (1 – exp[–t/ f]) + As x (1 – exp[–t/ s]), where Af and As are fractions of fast and slow inactivation components, and f and s are the time constants of fast and slow inactivation components, respectively. (C) Onset of slow inactivation. Time course of entry into the slow inactivation state was obtained by a double pulse protocol. Curves were fit with a single exponential equation: I/Imax = y0 + A x exp(–t/ ). (D) Closed-state inactivation. The transfer rate of Na+ channels from closed-state to inactivated closed-state without an intervening opening state was measured by a double pulse protocol. Time course for development of closed-state inactivation was fit with a single exponential equation: I/Imax = y0 + A x exp(–t/ ). The extent of closed-state inactivation was significantly less and the time constant larger in M1875T channels in comparison with WT.
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