Figure 6. Cooperative T618A subunit interactions mediate accelerated rate of hERG1 inactivation.

A, triple pulse voltage clamp protocol and corresponding currents recorded from oocytes expressing WT₄ or TA₄ hERG1 channels. Left panels show currents recorded in response to the indicated voltage steps. The first pulse was applied for 1 s and the second was 5 ms in duration for WT₄ and 4.5 ms for TA₄ channels. Expanded view of area designated by blue box is shown in right-hand panels. Inactivating current elicited during third pulse to +60 mV was fitted to a single exponential function (dotted red curves) to estimate τ_inact. B, plot of 1/τ_inact as a function of voltage for indicated concatenated tetramers (n = 4–7). C and D, estimated forward rate constants for inactivation (k) and k predicted by two models are plotted as a function of the number of T618A subunits in a concatenated tetramer for V_t of +60 mV (C) and +80 mV (D). Open square represents TA₁/WT₁/TA₁/WT₁ channels.