Figure 1.

Novel TRPM4 inhibitors block TRPM4 currents in HCT116 cells. (A) Chemical structure of CBA. (B) Chemical structure of LBA. (C) Chemical structure of NBA. (D) Whole-cell patch clamp data from HCT116. Currents were evoked with 10 µM Ca2⁺ in the patch pipette and normalized to cell size. Current density (CD), displayed as mean +/− SEM, is plotted versus time and 10 µM CBA was applied from 280–400 s. Inset: IV curves at t = 276 s and t = 396 s (n = 8). (E) Same as (D) for LBA (n = 5). (F) Same as (D) for NBA (n = 6). (G) Average TRPM4 CD +/− SEM was plotted against CBA concentrations (n = 9 for 0.01 µM, n = 7 for 0.1 µM, n = 9 for 1 µM, n = 10 for 3 µM, and n = 8 for 10 µM). Dose–response curve was fitted with a Hill equation and IC₅₀ value was 1.84 µM. (H) Average TRPM4 CD +/− SEM was plotted against LBA concentrations (n = 5 for 0.1 µM, n = 9 for 0.3 µM, n = 13 for 1 µM, n = 8 for 3 µM, and n = 5 for 10 µM). Dose–response curve was fitted with a Hill equation and IC₅₀ value was 1.84 µM. (I) Average TRPM4 CD +/− SEM was plotted against NBA concentrations (n = 6 for 0.001 µM, n = 9 0.01 µM, n = 9 for 0.03 µM, n = 6 for 0.1 µM, n = 13 for 0.3 µM, n = 5 for 1 µM, and n = 6 for 10 µM). Dose–response curve was fitted with a Hill equation and IC₅₀ value was 1.84 µM.