Fig. 3.

Separation of inhibiting and activating effects of A9C on TMEM16A, TMEM16A-Q645A, and -I637A channels. (A) Whole-cell currents recorded from HEK-293T cells expressing TMEM16A, TMEM16A-Q645A, or -I637A channels, as indicated. V_m was +70 mV, and [Ca²⁺]_i was 0, 0.1, or 0.3 μM, as indicated. Extracellular A9C (300 μM) was applied (“concentration jump”) as indicated by the horizontal bars. Dashed horizontal lines represent the zero-current level. The shaded gray bars indicate regions of the recording that were expanded in B. (B) The continuous red traces represent single exponential fits used to back-extrapolate the currents to obtain I_b (Left) and I_a (Right). (C) Mean current inhibition (I_b/I₀, Left) and activation (I_a/I₀, Right) plotted for each channel type in box plots, as indicated. The number of experiments was 6 to 10 in each case. *P < 0.05, compared to TMEM16A.