Figure 6.

Quantitative analyses of steady-state alkylamine block of wild-type and D172N mutant IRK1 channels. (A) Natural logarithm of K_d(0 mV) (determined as before [Guo and Lu, 2000a]; mean ± SEM; n = 6–10; all error bars within the symbols) for mono- and bis-alkyl-amines in wild-type and mutant channels, plotted against the number of methylene groups in the alkyl chain. The three lines are linear fits to the data, yielding (top to bottom) slopes of 0.68, 0.71, and 0.71, and Y-intercepts at “zero alkyl chain length” of −1.54, −1.96, and −4.93. The fourth (dotted) curve was drawn by hand. (B) Z_obs (determined as in Guo and Lu, 2000a) of wild-type and mutant channel block by alkyl-mono- and bis-amines plotted against chain length; mean ± SEM; n = 6–10; connected by straight lines. (C) An illustration of thermodynamic cycles (Hidalgo and MacKinnon, 1995). The four corners are K_ds (0 mV) of wild-type and mutant channels for mono- or bis-C2 and for a given mono- or bis-Cn. Ω = (^wtK_d ^C2 × ^mtK_d ^Cn)/(^mtK_d ^C2 × ^wtK_d ^Cn), where K_ds (all at 0 mV) are taken from A. (D) Ω values, computed as in C, plotted against chain length. Bis-C11 is not available commercially.