Figure 8. Independent M645C subunit interactions mediate accelerated rate of hERG1 inactivation.

A, triple pulse voltage clamp protocol and corresponding currents recorded from oocytes expressing WT₄ or MC₄ hERG1 channels. Left panels show currents recorded in response to the indicated voltage steps. The first pulse was 1 s in duration and the second was 5 ms in duration for WT₄ and 3.5 ms for MC₄ 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 with 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 = 4–10). C and D, estimated forward rate constants for inactivation (k) and k predicted by indicated models are plotted as a function of the number of M645C subunits in a concatenated tetramer at +60 mV (C) and +80 mV (D). Open square represents MC₁/WT₁/MC₁/WT₁ channels.