Figure 1.

[K + ] o -dependent inhibition of mutant KCNQ1 channels with altered inactivation. (A) Typical current traces of KCNQ1 channels in 20 mM [K+]o. Below IV traces the tail currents are shown enlarged to visualize inactivation. (B) The extent of the fast inactivation depends on prepulse voltage. The y axis represents the fraction of inactivated channels, n = 4–10; error bars represent ±SEM. (C) Inhibition of wild type and mutant KCNQ1 channels by K+o shown in A. Dashed line represents 0 current. Tail currents recorded in various [K+]o are shown enlarged. (D) Normalized mean peak currents over three continuous time points at five different [K+]o as indicated; n = 4–10, error bars represent ±SEM. (E) Concentration–response curves after correction of data are shown in D for theoretical values. Solid curves represent fits of the data to the Hill equation. Parameters of inhibition are shown in Table 1; n = 4–10, error bars represent ±SEM. (F) Correlation plot showing the relationship of [K+]o-induced inhibition of channels to their fractional inactivation at +60 mV. The y axis represents maximal inhibition obtained by fitting the Hill equation to the data (see Table 1). Detailed analysis for five other mutants is shown in Figs. S2 and S3. Solid line represents fit of data to linear function. Pearson correlation coefficient is −0.22, n = 4–10, error bars represent ±SEM.

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