Figure 4. Graded inhibition of hERG1 inactivation by S631A subunits.

A, representative current traces for SA₁/WT₃ and SA₄ concatenated tetramers recorded during pulses to indicated voltages. Oocytes were bathed in 98Na2K extracellular solution. B, fully activated I_tail–V_ret relationships for concatenated tetramers as indicated in the key in (C) (n = 5–9). Y-axis refers to mean WT₄ channel currents (in μA). To adjust for variable expression, the g_max for each mutant channel type was scaled to match the g_max for WT₄ channels. C, voltage dependence of inactivation for concatenated tetramers as indicated. Values of g/g_max at −90 mV (near E_rev) were omitted. Values of V_0.5 and z determined from fitting data to a Boltzmann function are summarized in Table 1. D and E, inactivation curves (g/g_max–V_ret relationships) of WT₄ and SA₄ channels (same as mean data plotted in C) together with curves predicted for three heterotypic channels by the independent model (D) and the standard cooperative model (E). F, ΔG_inact calculated from data (squares, n = 5–9) plotted as a function of the number of WT subunits contained in a concatenated tetramer is compared to ΔG_inact predicted by the indicated independent and cooperative models. Open square represents SA₁/WT₁/SA₁/WT₁ channels.