Fig. 8: Tail current increase in ML277 vs. inactivation of KCNQ1 mutants is reflected in single channels.

a Tail current response to ML277, data from Fig. 7c, on a log ordinate vs non-inactivated tail current fraction in the absence of ML277 (see inset) from Fig. 7e. Fitted correlation r_s = −0.86, P = 0.0001, Spearman rank coefficient. Linear trend line is shown. Inset panel shows control tail currents at −120 mV for WT and stated mutants. As an example, the initial peak of the WT tail (blue) is indicated, and also the fit back to the tail start to extract the fitted peak value. Values represent the mean ± SEM, n values as for Fig. 7c and e. b As for panel a except non-inactivated fraction was obtained in the presence of 1 μM ML277. L251A and G272C/T/L/V were unchanged from control solution (panel a) and for clarity are not replotted. Note that in some cases vertical and horizontal error bars fall within plotted symbols. c Voltage protocol and representative single-channel recordings of WT, S338A, and G272C KCNQ1 in control and 1 μM ML277 as indicated. Data filtered at 2 kHz at acquisition, and 200 Hz for presentation. Dotted lines denote zero pA (baseline) and 0.1 pA. No ML277 data were obtained for G272C. d Gaussian fits of amplitude event distributions for a blank sweep (gray), WT, S338A, and G272C sweeps, in control and ML277 as indicated. For WT, peaks were 0.02 in control, and 0.069 ± 0.003 pA in ML277, n = 4 cells. For S338A, peaks were 0.022 ± 0.002 in control (not shown) and 0.049 ± 0.003 pA in ML277, n = 3 cells. For G272C peaks were 0.040 ± 0.002 pA in control, n = 3 cells.